Is SRCAP p.Cys2372Arg (c.7114T>C) pathogenic?

SRCAP p.Cys2372Arg (c.7114T>C) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.2102); Rare (popmax 0.19%, sas).

How common is SRCAP p.Cys2372Arg (c.7114T>C) in the general population?

SRCAP p.Cys2372Arg (c.7114T>C) is rare (popmax 0.19%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Cys2372Arg (c.7114T>C)?

AlphaMissense predicts likely benign (score 0.2102) — an in-silico prediction, not a clinical call.

SRCAP p.Cys2372Arg

c.7114T>C · rs572129697 · VCV758111

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2102 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.19%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2102	likely benign
REVEL	0.254	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	22.3	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 0.19% South Asian · 173/91,088 alleles

Filtering AF 0.167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.0114% 184/1,614,010 alleles · rare exomes 174/1,461,856 · genomes 10/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.19%	527
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0112%	8,928
European (non-Finnish)	0.000254%	393,331

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.Cys2372Arg
Coding: c.7114T>C
MANE Select: NM_006662
dbSNP: rs572129697
Type: single nucleotide variant
Location: chr16:30737154 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2372: the 'disordered' region; a UniProt-annotated variant site (in dehmba)

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

Similar variants

SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter Pathogenic ★★ same type
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2748Ter Pathogenic ★★ same type
SRCAP p.Gln2407Ter Pathogenic ★★ same type
SRCAP p.Gln2419Ter Pathogenic ★★ same type
SRCAP p.Gln2665Ter Pathogenic/Likely pathogenic ★★ same type

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-cys2372arg (accessed [today's date]).

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