Is SRCAP p.Val305Ala (c.914T>C) pathogenic?

SRCAP p.Val305Ala (c.914T>C) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-26). AlphaMissense: ambiguous (0.3773); Very rare (popmax 0.00333%, amr); Associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities.

How common is SRCAP p.Val305Ala (c.914T>C) in the general population?

SRCAP p.Val305Ala (c.914T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Val305Ala (c.914T>C)?

AlphaMissense predicts ambiguous (score 0.3773) — an in-silico prediction, not a clinical call.

SRCAP p.Val305Ala

Q: What condition is associated with SRCAP p.Val305Ala (c.914T>C)?

SRCAP p.Val305Ala (c.914T>C) is associated with developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities, Floating-Harbor syndrome (ClinVar).

c.914T>C · VCV3580064

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

developmental delay, hypotonia, musculoskeletal defects, and behavioral abnormalities

Computational evidence

Protein change
AlphaMissense	0.3773	ambiguous
REVEL	0.187	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 127 bp · p 0.0011 · regional, not allelic
Overall
CADD	24.4	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 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,110 alleles · very rare exomes 2/1,461,892 · genomes 0/152,218 · joint denominator

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.Val305Ala
Coding: c.914T>C
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30709908 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 305: the 'disordered' region

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.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
SRCAP p.Gln2419Ter Pathogenic ★★ same condition
SRCAP p.Gln2665Ter Pathogenic/Likely 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-val305ala (accessed [today's date]).

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