Is SRCAP p.Pro2487Arg (c.7460C>G) pathogenic?

SRCAP p.Pro2487Arg (c.7460C>G) is classified Likely benign in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely benign (0.1271); Ultra-rare (popmax 0.0165%, mid).

How common is SRCAP p.Pro2487Arg (c.7460C>G) in the general population?

SRCAP p.Pro2487Arg (c.7460C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Pro2487Arg (c.7460C>G)?

AlphaMissense predicts likely benign (score 0.1271) — an in-silico prediction, not a clinical call.

SRCAP p.Pro2487Arg

c.7460C>G · rs775147297 · VCV2672628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1271 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1271	likely benign
REVEL	0.239	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
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	11.6	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 0.0165% Middle Eastern · 1/6,050 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000438% 7/1,599,214 alleles · ultra-rare exomes 6/1,447,016 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
Remaining individualsnot grpmax-eligible	0.00323%	30,971
South Asian	0.00221%	45,332
European (non-Finnish)	0.000171%	583,642

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.Pro2487Arg
Coding: c.7460C>G
MANE Select: NM_006662
dbSNP: rs775147297
Type: single nucleotide variant
Location: chr16:30737500 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2487: 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.Pro2487Ala Uncertain significance ★★ ⚠ same residue
SRCAP p.Pro2487Thr Uncertain significance ★ ⚠ same residue
SRCAP p.Pro2487Leu 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

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-pro2487arg (accessed [today's date]).

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