# NM_006662.3(SRCAP):c.1636GAT[2] (p.Asp548del)

https://sugi.bio/variant/srcap-p-asp548del

## Summary

**SRCAP p.Asp548del (c.1636GAT[2])** is classified **Uncertain significance** in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

**At a glance:** Uncertain significance · review: Single submitter · 1 submitter · 2 linked conditions

## For patients & families {#patients}

This is a change in the SRCAP gene that is currently of uncertain significance — a definitive interpretation has not yet been established, submitted by 1 submitter, and is linked to developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

*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 | [SRCAP](https://sugi.bio/atlas/gene/SRCAP/) |
| Protein change (HGVS p.) | p.Asp548del |
| Coding change (HGVS c.) | c.1636GAT[2] |
| MANE Select transcript | [NM_006662](https://www.ncbi.nlm.nih.gov/nuccore/NM_006662) |
| Variant type | Microsatellite |
| Location | chr16:30711978-30711980 (GRCh38) |
| ClinVar | [VCV3580081](https://www.ncbi.nlm.nih.gov/clinvar/variation/3580081/) |

**All HGVS expressions:** `NC_000016.10:g.30711978GAT[2]`, `NC_000016.9:g.30723299GAT[2]`, `NG_032135.1:g.17838GAT[2]`, `NG_032135.2:g.17809GAT[2]`, `NM_006662.3:c.1636GAT[2]`, `NM_006662.3:c.1642_1644del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -0.887, GERP -2.96 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **in-frame indel**.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no microsatellite variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.

*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}

**SRCAP** population constraint: LOEUF 0.223, pLI 1, missense-Z 3.6475; ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *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):

- **Floating-Harbor syndrome** — Definitive (AD)

## Protein context {#protein}

Residue **548** lies in a UniProt-annotated variant site (in dehmba).

**22 experimental structure(s)** (PDB): [6IGM](https://www.rcsb.org/structure/6IGM), [8X15](https://www.rcsb.org/structure/8X15), [8X19](https://www.rcsb.org/structure/8X19), [8X1C](https://www.rcsb.org/structure/8X1C), [9CA7](https://www.rcsb.org/structure/9CA7), [9CA8](https://www.rcsb.org/structure/9CA8) — incl. mutant structure 9UBD.

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

*Describes the biological roles of SRCAP (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:** SRCAP's established molecular role includes transcription coactivator activity.


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

**Molecular function:** transcription coactivator activity, ATP-dependent chromatin remodeler activity.

**Biological process:** positive regulation of transcription by RNA polymerase II, cAMP/PKA signal transduction.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-01-02.

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

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Fulgent Genetics, Fulgent Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-01-02 |

## Associated conditions {#conditions}

[developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities](https://sugi.bio/atlas/disease/developmental-delay-hypotonia-musculoskeletal-defects-and-behavioral-abnormalities/), [Floating-Harbor syndrome](https://sugi.bio/atlas/disease/floating-harbor-syndrome/).

**Reported phenotype names (ClinVar):** Developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome, SRCAP-Related Floating-Harbor Syndrome, Short stature with delayed bone age, expressive language delay, a triangular face with a prominent nose and deep-set eyes, Pelletier-Leisti syndrome.

## Similar variants {#similar}

Related SRCAP variant pages (same residue, condition, or type): [SRCAP p.Asp548Gly](/variant/srcap-p-asp548gly), [SRCAP p.Gln2770del](/variant/srcap-p-gln2770del), [SRCAP p.Glu3182del](/variant/srcap-p-glu3182del), [SRCAP p.Pro2488del](/variant/srcap-p-pro2488del), [SRCAP p.Ser2576del](/variant/srcap-p-ser2576del), [SRCAP p.Glu2405fs](/variant/srcap-p-glu2405fs), [SRCAP p.Val2646fs](/variant/srcap-p-val2646fs), [SRCAP p.Arg2768_Gln2769insArg](/variant/srcap-p-arg2768-gln2769insarg).

### 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 3580081). 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.*