# NM_006268.5(DPF2):c.19A>G (p.Asn7Asp)

https://sugi.bio/variant/dpf2-p-asn7asp

## Summary

**DPF2 p.Asn7Asp (c.19A>G)** is classified **Uncertain significance** in DPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). AlphaMissense: ambiguous (0.3852); Absent from gnomAD v4.1; Associated with DPF2-related disorder.

**At a glance:** Uncertain significance · review: Single submitter · rsID rs1197539414 · 1 submitter · 1 linked condition · AlphaMissense ambiguous · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the DPF2 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter, and is linked to DPF2-related disorder.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DPF2](https://sugi.bio/atlas/gene/DPF2/) |
| Protein change (HGVS p.) | p.Asn7Asp |
| Coding change (HGVS c.) | c.19A>G |
| MANE Select transcript | [NM_006268](https://www.ncbi.nlm.nih.gov/nuccore/NM_006268) |
| dbSNP | [rs1197539414](https://www.ncbi.nlm.nih.gov/snp/rs1197539414/) |
| Variant type | single nucleotide variant |
| Location | chr11:65333905-65333905 (GRCh38) |
| ClinVar | [VCV2632651](https://www.ncbi.nlm.nih.gov/clinvar/variation/2632651/) |

**All HGVS expressions:** `NC_000011.10:g.65333905A>G`, `NC_000011.9:g.65101376A>G`, `NM_001330308.2:c.19A>G`, `NM_006268.5:c.19A>G`

## Computational & population evidence {#evidence}

**Concordance:** AlphaMissense and REVEL make no call here — the available evidence is described below.

- AlphaMissense **ambiguous** (0.3852) — no call either way
- REVEL 0.33 (indeterminate)
- SaProt LLR -3.762 (tolerated)
- Conservation: phyloP 10.8, GERP 1.7, phastCons 1 — highly conserved
- CADD: **PHRED 25.7**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 0.83** across the covering region of the MANE Select transcript (65,333,887–65,344,050), spanning 10,163 bp. Chi-square p 0.0043. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (A>T, Δ0.51 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**DPF2** population constraint: LOEUF 0.287, pLI 1, missense-Z 3.3606. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Coffin-Siris syndrome** — Definitive (AD)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 69.62, 30% of residues very-high.

**9 experimental structure(s)** (PDB): [3IUF](https://www.rcsb.org/structure/3IUF), [5B79](https://www.rcsb.org/structure/5B79), [5VDC](https://www.rcsb.org/structure/5VDC), [6LTH](https://www.rcsb.org/structure/6LTH), [6LTJ](https://www.rcsb.org/structure/6LTJ), [9RL4](https://www.rcsb.org/structure/9RL4).

## What this gene does {#gene-function}

*Describes the biological roles of DPF2 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** DPF2's established molecular role includes histone H3K14ac reader activity.


### Pathways affected {#pathways}

DPF2 participates in **6 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Formation of the canonical BAF (cBAF) complex](https://reactome.org/content/detail/R-HSA-9933937) | curated |
| [Formation of the embryonic stem cell BAF (esBAF) complex](https://reactome.org/content/detail/R-HSA-9933946) | curated |
| [Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF)](https://reactome.org/content/detail/R-HSA-9934037) | electronic |
| [Regulation of MITF-M-dependent genes involved in pigmentation](https://reactome.org/content/detail/R-HSA-9824585) | electronic |
| [Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)](https://reactome.org/content/detail/R-HSA-9845323) | electronic |
| [Somatic hypermutation of immunoglobulin genes](https://reactome.org/content/detail/R-HSA-9938024) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** histone H3K14ac reader activity, histone H4K16ac reader activity.

**Biological process:** negative regulation of myeloid progenitor cell differentiation.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2023-07-18.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Uncertain significance | criteria provided, single submitter | clinical testing | 2023-07-18 |

## Associated conditions {#conditions}

[DPF2-related disorder](https://sugi.bio/atlas/disease/dpf2-related-disorder/).

**Reported phenotype names (ClinVar):** DPF2-related disorder, DPF2-related condition.

## Similar variants {#similar}

Related DPF2 variant pages (same residue, condition, or type): [DPF2 p.Asn7=](/variant/dpf2-p-asn7), [DPF2 p.Glu120Gly](/variant/dpf2-p-glu120gly), [DPF2 p.Gly13Arg](/variant/dpf2-p-gly13arg), [DPF2 c.637+541C>T](/variant/dpf2-c-637-plus-541c-t), [DPF2 p.Arg35=](/variant/dpf2-p-arg35), [DPF2 p.Leu167=](/variant/dpf2-p-leu167), [DPF2 c.904+1G>A](/variant/dpf2-c-904-plus-1g-a), [DPF2 p.Arg350His](/variant/dpf2-p-arg350his).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2632651). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*