Is SRCAP p.Asp81His (c.241G>C) pathogenic?

SRCAP p.Asp81His (c.241G>C) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-05-24). AlphaMissense: likely benign (0.1597); Ultra-rare (popmax 0.0657%, mid); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Asp81His (c.241G>C)?

SRCAP p.Asp81His (c.241G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Asp81His (c.241G>C) in the general population?

SRCAP p.Asp81His (c.241G>C) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Asp81His (c.241G>C)?

AlphaMissense predicts likely benign (score 0.1597) — an in-silico prediction, not a clinical call.

SRCAP p.Asp81His

c.241G>C · rs1339584247 · VCV2551183

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1597 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1597	likely benign
REVEL	0.335	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,462 bp · p 0.64 · regional, not allelic
Overall
CADD	23.5	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.000682% 11/1,614,042 alleles · ultra-rare exomes 10/1,461,822 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.000424%	236,000

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.Asp81His
Coding: c.241G>C
MANE Select: NM_006662
dbSNP: rs1339584247
Type: single nucleotide variant
Location: chr16:30704250 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Asp81Gly Uncertain significance ★★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1570Thr Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1584Gly Uncertain significance ★★ same condition
SRCAP p.Ala1985Thr Uncertain significance ★★ same condition
SRCAP p.Ala2699Val Uncertain significance ★★ ⚠ same condition

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-asp81his (accessed [today's date]).

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