Is SRCAP p.Arg2768Gln (c.8303G>A) pathogenic?

SRCAP p.Arg2768Gln (c.8303G>A) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely benign (0.1946); Very rare (popmax 0.00476%, sas).

How common is SRCAP p.Arg2768Gln (c.8303G>A) in the general population?

SRCAP p.Arg2768Gln (c.8303G>A) is very rare (popmax 0.00476%, sas) (gnomAD).

What do computational predictors say about SRCAP p.Arg2768Gln (c.8303G>A)?

AlphaMissense predicts likely benign (score 0.1946) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2768Gln

c.8303G>A · rs748197121 · VCV2871718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00476%, sas)

Computational evidence

Protein change
AlphaMissense	0.1946	likely benign
REVEL	0.365	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	25.3	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 0.00476% South Asian · 4/84,056 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000949%

Overall 0.000573% 9/1,570,820 alleles · very rare exomes 8/1,418,624 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00476%	21,014
East Asian	0.00224%	44,552
European (non-Finnish)	0.000345%	289,617

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.Arg2768Gln
Coding: c.8303G>A
MANE Select: NM_006662
dbSNP: rs748197121
Type: single nucleotide variant
Location: chr16:30738343 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2768: 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.Arg2768= Likely benign ★★ same residue
SRCAP p.Arg2768Leu Uncertain significance ★ same residue
SRCAP p.Arg2768_Gln2769insArg Uncertain significance ★ same residue
SRCAP p.Arg2768_Gln2769insArgArg Uncertain significance ★ 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

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-arg2768gln (accessed [today's date]).

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