Is SRCAP p.Val376Met (c.1126G>A) pathogenic?

SRCAP p.Val376Met (c.1126G>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-24). AlphaMissense: likely benign (0.0973); Absent from gnomAD v4.1; Associated with SRCAP-related disorder.

What condition is associated with SRCAP p.Val376Met (c.1126G>A)?

SRCAP p.Val376Met (c.1126G>A) is associated with SRCAP-related disorder (ClinVar).

How common is SRCAP p.Val376Met (c.1126G>A) in the general population?

SRCAP p.Val376Met (c.1126G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Val376Met (c.1126G>A)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

SRCAP p.Val376Met

c.1126G>A · rs760104009 · VCV2413299

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

SRCAP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.56	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.2	GERP -2.1, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	16.7	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRCAP
Protein: p.Val376Met
Coding: c.1126G>A
MANE Select: NM_006662
dbSNP: rs760104009
Type: single nucleotide variant
Location: chr16:30710120 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 376: the 'disordered' region

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

Disease context

SRCAP-related disorder

Similar variants

SRCAP p.Val376= Uncertain significance ★ same residue
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln3043His Uncertain significance ★★ ⚠ same condition
SRCAP p.Gln3202His Uncertain significance ★★ same condition
SRCAP p.Leu2652Arg Uncertain significance ★★ same condition
SRCAP p.Pro1728Ala Uncertain significance ★★ ⚠ 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-val376met (accessed [today's date]).

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