Is SRCAP p.Thr1767Met (c.5300C>T) pathogenic?

SRCAP p.Thr1767Met (c.5300C>T) is classified Likely benign in SRCAP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.1256); Ultra-rare (popmax 0.065%, amr).

How common is SRCAP p.Thr1767Met (c.5300C>T) in the general population?

SRCAP p.Thr1767Met (c.5300C>T) is ultra-rare (popmax 0.065%, amr) (gnomAD).

What do computational predictors say about SRCAP p.Thr1767Met (c.5300C>T)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

SRCAP p.Thr1767Met

c.5300C>T · rs181491375 · VCV436856

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, amr)

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.293	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 8,776 bp · p 0.24 · regional, not allelic
Overall
CADD	21.5	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 0.065% Admixed American · 39/60,022 alleles

Filtering AF 0.0488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.0175% 282/1,614,138 alleles · ultra-rare exomes 264/1,461,786 · genomes 18/152,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.065%	1,539
South Asian	0.0516%	1,938
Remaining individualsnot grpmax-eligible	0.0176%	5,682
European (non-Finnish)	0.0147%	6,821
African / African-American	0.00799%	12,510
Finnishnot grpmax-eligible	0.00625%	15,994
East Asian	0.00446%	22,440

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.Thr1767Met
Coding: c.5300C>T
MANE Select: NM_006662
dbSNP: rs181491375
Type: single nucleotide variant
Location: chr16:30724724 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1767: 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.Thr1767Arg Uncertain significance ★ ⚠ same residue
SRCAP p.Thr1767= 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
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-thr1767met (accessed [today's date]).

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