# NM_013379.3(DPP7):c.620C>T (p.Ala207Val)

https://sugi.bio/variant/dpp7-p-ala207val

## Summary

**DPP7 p.Ala207Val (c.620C>T)** is classified **Uncertain significance** in DPP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.0011%, sas).

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter · AlphaMissense likely benign · very rare (popmax 0.0011%, sas)

## For patients & families {#patients}

This is a change in the DPP7 gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter.

*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 | [DPP7](https://sugi.bio/atlas/gene/DPP7/) |
| Protein change (HGVS p.) | p.Ala207Val |
| Coding change (HGVS c.) | c.620C>T |
| MANE Select transcript | [NM_013379](https://www.ncbi.nlm.nih.gov/nuccore/NM_013379) |
| Variant type | single nucleotide variant |
| Location | chr9:137113362-137113362 (GRCh38) |
| ClinVar | [VCV4244516](https://www.ncbi.nlm.nih.gov/clinvar/variation/4244516/) |

**All HGVS expressions:** `NC_000009.11:g.140007814G>A`, `NC_000009.12:g.137113362G>A`, `NM_001438108.1:c.686C>T`, `NM_001438109.1:c.686C>T`, `NM_001438110.1:c.620C>T`, `NM_013379.3:c.620C>T`

## Computational & population evidence {#evidence}

**Concordance:** ClinVar classifies this **uncertain**; the computational predictors unanimously lean **tolerated** — a triage signal, not a reclassification.

- AlphaMissense **likely benign** (0.1123)
- REVEL 0.122 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -7.931 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- SpliceAI predicts **donor gain** (Δ 0.25) — a splice-altering prediction on an uncertain variant — a signal for review
- Conservation: phyloP 0.063, GERP -2.93 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 18.86**. 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 1.17** across the covering region of the MANE Select transcript (137,110,651–137,114,006), spanning 3,355 bp. Chi-square p 5.6e-05. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI deltas (raw): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.25**. Largest is donor gain.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.25**.
- Population frequency (gnomAD v4.1): grpmax **0.0011%** (sas) · FAF95 0.000183% · FAF99 0.00012% · 1/91,056 in the highest group · 7/1,611,412 alleles overall — very rare (popmax 0.0011%, sas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| South Asian (grpmax) | 0.0011% | 91,056 |
| European (non-Finnish) | 0.000509% | 196,455 |

*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}

**DPP7** population constraint: LOEUF 1.707, pLI 5.6935e-33, missense-Z -2.2504. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **207** lies in an α-helix.

AlphaFold model confidence (whole protein): pLDDT 94.44, 92% of residues very-high.

**3 experimental structure(s)** (PDB): [3JYH](https://www.rcsb.org/structure/3JYH), [3N0T](https://www.rcsb.org/structure/3N0T), [4EBB](https://www.rcsb.org/structure/4EBB).

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

*Describes the biological roles of DPP7 (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.*


### Pathways affected {#pathways}

DPP7 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-06-25.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2025-06-25 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related DPP7 variant pages (same residue, condition, or type): [DPP7 p.Arg17=](/variant/dpp7-p-arg17), [DPP7 c.322-1G>T](/variant/dpp7-c-322-minus-1g-t), [DPP7 p.Ala118Gly](/variant/dpp7-p-ala118gly), [DPP7 p.Ala118Val](/variant/dpp7-p-ala118val), [DPP7 p.Ala136Val](/variant/dpp7-p-ala136val), [DPP7 p.Ala139Gly](/variant/dpp7-p-ala139gly), [DPP7 p.Ala13Val](/variant/dpp7-p-ala13val), [DPP7 p.Ala158Asp](/variant/dpp7-p-ala158asp).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); 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 2026-10-14); 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 4244516). 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.*