Is SRCAP p.Arg2297Trp (c.6889C>T) pathogenic?

SRCAP p.Arg2297Trp (c.6889C>T) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.66); Absent from gnomAD v4.1.

How common is SRCAP p.Arg2297Trp (c.6889C>T) in the general population?

SRCAP p.Arg2297Trp (c.6889C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Arg2297Trp (c.6889C>T)?

AlphaMissense predicts likely pathogenic (score 0.66) — an in-silico prediction, not a clinical call.

SRCAP p.Arg2297Trp

c.6889C>T · rs1398741863 · VCV2574958

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.66 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.66	likely pathogenic
REVEL	0.487	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.48, phastCons 0.98
Regional constraint	o/e 0.60	unconstrained · MANE · 918 bp · p 1.2e-06 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SRCAP
Protein: p.Arg2297Trp
Coding: c.6889C>T
MANE Select: NM_006662
dbSNP: rs1398741863
Type: single nucleotide variant
Location: chr16:30736359 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2297: the 'disordered' region; 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.Arg2297= Likely benign ★ same residue
SRCAP p.Arg2297fs Likely pathogenic 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
SRCAP p.Arg2748Ter Pathogenic ★★ same type
SRCAP p.Gln2407Ter 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-arg2297trp (accessed [today's date]).

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