Is CAPS p.Thr175Met (c.524C>T) pathogenic?

CAPS p.Thr175Met (c.524C>T) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-18). AlphaMissense: likely benign (0.1711); Ultra-rare (popmax 0.0168%, mid).

How common is CAPS p.Thr175Met (c.524C>T) in the general population?

CAPS p.Thr175Met (c.524C>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about CAPS p.Thr175Met (c.524C>T)?

AlphaMissense predicts likely benign (score 0.1711) — an in-silico prediction, not a clinical call.

CAPS p.Thr175Met

c.524C>T · rs761339517 · VCV2525759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1711 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1711	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -11.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T261M vs ClinVar T175M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,958 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00174% 28/1,612,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,958
East Asian	0.00668%	14,961
European (non-Finnish)	0.00186%	53,630
Remaining individualsnot grpmax-eligible	0.0016%	62,446
South Asian	0.0011%	91,062

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: CAPS
Protein: p.Thr175Met
Coding: c.524C>T
MANE Select: NM_003716 · reported on NM_004058
dbSNP: rs761339517
Type: single nucleotide variant
Location: chr19:5915276 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB

Full CAPS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CADPS p.Ser203= Benign ★★ same type
CADPS p.Tyr579= Benign ★★ same type
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CADPS c.3477+2T>G Uncertain significance ★ same type
CADPS p.Ala1047Thr Uncertain significance ★ ⚠ same type
CADPS p.Ala1057Val Uncertain significance ★ ⚠ same type
CADPS p.Ala1114Thr Uncertain significance ★ ⚠ 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/caps-p-thr175met (accessed [today's date]).

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