Is SRCAP p.Asp942Asn (c.2824G>A) pathogenic?

SRCAP p.Asp942Asn (c.2824G>A) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: ambiguous (0.3849); Very rare (popmax 0.00224%, eas); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Asp942Asn (c.2824G>A) in the general population?

SRCAP p.Asp942Asn (c.2824G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Asp942Asn (c.2824G>A)?

AlphaMissense predicts ambiguous (score 0.3849) — an in-silico prediction, not a clinical call.

SRCAP p.Asp942Asn

Q: What condition is associated with SRCAP p.Asp942Asn (c.2824G>A)?

SRCAP p.Asp942Asn (c.2824G>A) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.2824G>A · VCV3580101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.3849	ambiguous
REVEL	0.582	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.32	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 4,608 bp · p 6.7e-06 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,672 alleles

Overall 0.000124% 2/1,608,212 alleles · very rare exomes 1/1,455,982 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,672
European (non-Finnish)	8.51e-05%	1,175,125

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SRCAP
Protein: p.Asp942Asn
Coding: c.2824G>A
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30720168 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 942: a UniProt-annotated variant site (in dehmba)

Full SRCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Floating-Harbor syndrome

Similar variants

SRCAP p.Asp942Gly Uncertain significance ★ ⚠ same residue
SRCAP p.Asp942Val Uncertain significance ★ ⚠ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/srcap-p-asp942asn (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown