Is SRCAP p.Arg326Cys (c.976C>T) pathogenic?

SRCAP p.Arg326Cys (c.976C>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1497); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Arg326Cys (c.976C>T)?

SRCAP p.Arg326Cys (c.976C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Arg326Cys (c.976C>T) in the general population?

SRCAP p.Arg326Cys (c.976C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Arg326Cys (c.976C>T)?

AlphaMissense predicts likely benign (score 0.1497) — an in-silico prediction, not a clinical call.

SRCAP p.Arg326Cys

c.976C>T · VCV3449219

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1497 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1497	likely benign
REVEL	0.426	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.80 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 127 bp · p 0.0011 · regional, not allelic
Overall
CADD	27.9	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 0.00267% African / African-American · 2/74,896 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,032 alleles · very rare exomes 1/1,461,890 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,448
European (non-Finnish)	8.47e-05%	1,180,038

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.Arg326Cys
Coding: c.976C>T
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30709970 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 326: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Arg326Leu Conflicting classifications of pathogenicity ★ same residue
SRCAP p.Arg326His Uncertain significance ★ ⚠ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1584Gly Uncertain significance ★★ same condition
SRCAP p.Ala1985Thr 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-arg326cys (accessed [today's date]).

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