Is SRCAP p.Met1980Ile (c.5940G>A) pathogenic?

SRCAP p.Met1980Ile (c.5940G>A) is classified Likely pathogenic in SRCAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). AlphaMissense: likely pathogenic (0.8435); Absent from gnomAD v4.1.

How common is SRCAP p.Met1980Ile (c.5940G>A) in the general population?

SRCAP p.Met1980Ile (c.5940G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRCAP p.Met1980Ile (c.5940G>A)?

AlphaMissense predicts likely pathogenic (score 0.8435) — an in-silico prediction, not a clinical call.

SRCAP p.Met1980Ile

c.5940G>A · rs1249494343 · VCV2096163

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8435 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.8435	likely pathogenic ✓ concordant with ClinVar
REVEL	0.281	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	22.1	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.Met1980Ile
Coding: c.5940G>A
MANE Select: NM_006662
dbSNP: rs1249494343
Type: single nucleotide variant
Location: chr16:30729385 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1980: 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.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
SRCAP p.Gln2419Ter Pathogenic ★★ same type
SRCAP p.Gln2665Ter Pathogenic/Likely 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-met1980ile (accessed [today's date]).

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