Is SRCAP p.Arg2828His (c.8483G>A) pathogenic?

SRCAP p.Arg2828His (c.8483G>A) is classified Conflicting classifications of pathogenicity in SRCAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.0964); Ultra-rare (popmax 0.0134%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Arg2828His (c.8483G>A)?

SRCAP p.Arg2828His (c.8483G>A) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Arg2828His (c.8483G>A) in the general population?

SRCAP p.Arg2828His (c.8483G>A) is ultra-rare (popmax 0.0134%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Arg2828His (c.8483G>A)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2828His

c.8483G>A · rs148477226 · VCV1362685

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.326	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 2,598 bp · p 0.058 · regional, not allelic
Overall
CADD	22.7	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 0.0134% European (non-Finnish) · 158/1,178,944 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.0106% 171/1,611,856 alleles · ultra-rare exomes 165/1,459,728 · genomes 6/152,128 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0134%	7,462
Remaining individualsnot grpmax-eligible	0.00961%	10,401
Admixed American	0.00503%	19,877
South Asian	0.0033%	30,273
African / African-American	0.00134%	74,838

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.Arg2828His
Coding: c.8483G>A
MANE Select: NM_006662
dbSNP: rs148477226
Type: single nucleotide variant
Location: chr16:30738523 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2828: 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

Disease context

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

Similar variants

SRCAP p.Arg2828Cys Benign/Likely benign ★★ same residue
SRCAP p.Arg2828Ser 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

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-arg2828his (accessed [today's date]).

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