Is SRCAP p.Arg503Gln (c.1508G>A) pathogenic?

SRCAP p.Arg503Gln (c.1508G>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-05). AlphaMissense: likely benign (0.0538); Very rare (popmax 0.00446%, eas).

How common is SRCAP p.Arg503Gln (c.1508G>A) in the general population?

SRCAP p.Arg503Gln (c.1508G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about SRCAP p.Arg503Gln (c.1508G>A)?

AlphaMissense predicts likely benign (score 0.0538) — an in-silico prediction, not a clinical call.

SRCAP p.Arg503Gln

c.1508G>A · rs774882612 · VCV1468620

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0538	likely benign
REVEL	0.176	moderately 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 3.8	GERP -0.64, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 2,095 bp · p 0.41 · regional, not allelic
Overall
CADD	14.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.0031% 50/1,613,690 alleles · very rare exomes 48/1,461,680 · genomes 2/152,010 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
South Asian	0.00439%	22,769
African / African-American	0.00401%	24,946
Admixed American	0.00333%	29,991
European (non-Finnish)	0.00314%	31,892
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00157%	63,846

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.Arg503Gln
Coding: c.1508G>A
MANE Select: NM_006662
dbSNP: rs774882612
Type: single nucleotide variant
Location: chr16:30711850 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 503: a UniProt-annotated variant site (in dehmba); the 'disordered' region

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

Similar variants

SRCAP p.Arg503Gly Uncertain significance ★★ ⚠ same residue
SRCAP p.Arg503Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
SRCAP p.Arg503= 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-arg503gln (accessed [today's date]).

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