Is SRCAP p.Arg2002Ser (c.6004C>A) pathogenic?

SRCAP p.Arg2002Ser (c.6004C>A) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely benign (0.3317); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with SRCAP p.Arg2002Ser (c.6004C>A)?

SRCAP p.Arg2002Ser (c.6004C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SRCAP p.Arg2002Ser (c.6004C>A) in the general population?

SRCAP p.Arg2002Ser (c.6004C>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about SRCAP p.Arg2002Ser (c.6004C>A)?

AlphaMissense predicts likely benign (score 0.3317) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2002Ser

c.6004C>A · rs768710823 · VCV1985193

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3317 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3317	likely benign
REVEL	0.322	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	23.0	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,614,102 alleles · ultra-rare exomes 25/1,461,894 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.00203%	49,169
African / African-American	0.00133%	74,930

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.Arg2002Ser
Coding: c.6004C>A
MANE Select: NM_006662
dbSNP: rs768710823
Type: single nucleotide variant
Location: chr16:30729449 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2002: an α-helix; a UniProt-annotated variant site (in dehmba)

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.Arg2002Cys Uncertain significance ★ same residue
SRCAP p.Arg2002Gly Uncertain significance ★ ⚠ same residue
SRCAP p.Arg2002His Conflicting classifications of pathogenicity ★ ⚠ same residue
SRCAP p.Arg2002Leu Uncertain significance ★ same residue
SRCAP p.Arg2002= Likely benign ★ same residue
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Ala1152Val Uncertain significance ★★ ⚠ same condition
SRCAP p.Ala1161Thr 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-arg2002ser (accessed [today's date]).

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