Is SRCAP p.Arg2737Trp (c.8209C>T) pathogenic?

SRCAP p.Arg2737Trp (c.8209C>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-03). AlphaMissense: likely benign (0.1726); Ultra-rare (popmax 0.0167%, amr).

How common is SRCAP p.Arg2737Trp (c.8209C>T) in the general population?

SRCAP p.Arg2737Trp (c.8209C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Arg2737Trp (c.8209C>T)?

AlphaMissense predicts likely benign (score 0.1726) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2737Trp

c.8209C>T · VCV3375033

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Computational evidence

Protein change
AlphaMissense	0.1726	likely benign
REVEL	0.363	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -3.2, phastCons 0.89
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	20.2	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 0.0167% Admixed American · 10/59,904 alleles

Filtering AF 0.00901% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.0018% 29/1,612,820 alleles · ultra-rare exomes 26/1,460,602 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,990
African / African-American	0.00267%	37,455
Remaining individualsnot grpmax-eligible	0.0016%	62,410
European (non-Finnish)	0.00136%	73,706

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.Arg2737Trp
Coding: c.8209C>T
MANE Select: NM_006662
Type: single nucleotide variant
Location: chr16:30738249 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2737: the 'disordered' region; 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.Arg2737Gln Uncertain significance ★★ ⚠ same residue
SRCAP p.Arg2737Gly Uncertain significance ★★ ⚠ same residue
SRCAP p.Arg2737= Conflicting classifications of pathogenicity ★ 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-arg2737trp (accessed [today's date]).

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