Is SRCAP p.Ser2524Cys (c.7571C>G) pathogenic?

SRCAP p.Ser2524Cys (c.7571C>G) is classified Benign/Likely benign in SRCAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1074); Low-frequency (popmax 2.32%, afr).

How common is SRCAP p.Ser2524Cys (c.7571C>G) in the general population?

SRCAP p.Ser2524Cys (c.7571C>G) is low-frequency (popmax 2.32%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ser2524Cys (c.7571C>G)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

SRCAP p.Ser2524Cys

c.7571C>G · rs75125670 · VCV596363

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.32%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.28	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 5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	19.61	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 2.32% African / African-American · 1,744/75,018 alleles

Filtering AF 2.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 0.123% 1,988/1,614,040 alleles · low-frequency exomes 991/1,461,780 · genomes 997/152,260 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.32%	43
Admixed American	0.195%	513
Remaining individualsnot grpmax-eligible	0.163%	613
Middle Eastern	0.0825%	1,212
South Asian	0.00769%	13,011
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00102%	98,335

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.Ser2524Cys
Coding: c.7571C>G
MANE Select: NM_006662
dbSNP: rs75125670
Type: single nucleotide variant
Location: chr16:30737611 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2524: a UniProt-annotated variant site (in dehmba); a UniProt-annotated variant site (in flhs)

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

Similar variants

SRCAP p.Ser2524= Likely benign ★ same residue
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

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-ser2524cys (accessed [today's date]).

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