Is SRCAP p.Arg2002Cys (c.6004C>T) pathogenic?

SRCAP p.Arg2002Cys (c.6004C>T) is classified Uncertain significance in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-29). AlphaMissense: likely benign (0.1383); Very rare (popmax 0.00322%, nfe).

How common is SRCAP p.Arg2002Cys (c.6004C>T) in the general population?

SRCAP p.Arg2002Cys (c.6004C>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

What do computational predictors say about SRCAP p.Arg2002Cys (c.6004C>T)?

AlphaMissense predicts likely benign (score 0.1383) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2002Cys

c.6004C>T · VCV3605274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1383	likely benign
REVEL	0.46	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	24.8	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 0.00322% European (non-Finnish) · 38/1,180,050 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00273% 44/1,614,102 alleles · very rare exomes 43/1,461,894 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,054
Finnishnot grpmax-eligible	0.00312%	32,021
African / African-American	0.00267%	37,465
East Asian	0.00223%	44,896
South Asian	0.0011%	91,088

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.Arg2002Cys
Coding: c.6004C>T
MANE Select: NM_006662
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

Similar variants

SRCAP p.Arg2002Ser 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.Arg2329Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same type
SRCAP p.Arg2444Ter 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-arg2002cys (accessed [today's date]).

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