Is CAPS2 p.Phe429Val (c.1285T>G) pathogenic?

CAPS2 p.Phe429Val (c.1285T>G) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.2588); Very rare (popmax 0.00786%, sas).

How common is CAPS2 p.Phe429Val (c.1285T>G) in the general population?

CAPS2 p.Phe429Val (c.1285T>G) is very rare (popmax 0.00786%, sas) (gnomAD).

What do computational predictors say about CAPS2 p.Phe429Val (c.1285T>G)?

AlphaMissense predicts likely benign (score 0.2588) — an in-silico prediction, not a clinical call.

CAPS2 p.Phe429Val

c.1285T>G · rs569221789 · VCV3137249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2588 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00786%, sas)

Computational evidence

Protein change
AlphaMissense	0.2588	likely benign
REVEL	0.317	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Overall
CADD	23.1	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 F486V vs ClinVar F429V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00786% South Asian · 7/89,038 alleles

Filtering AF 0.00366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00259%

Overall 0.000498% 8/1,605,648 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00786%	12,720
Remaining individualsnot grpmax-eligible	0.00161%	62,142

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: CAPS2
Protein: p.Phe429Val
Coding: c.1285T>G
MANE Select: NM_017954 · reported on NM_001355024
dbSNP: rs569221789
Type: single nucleotide variant
Location: chr12:75285077 (GRCh38)
Structure: AlphaFold pLDDT 79.91
Residue 429: the c2 domain

Full CAPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CADPS2 c.3718-15A>C Benign ★★ same type
CADPS2 p.Ala298Thr Benign ★★ same type
CADPS2 p.Asp1088Asn Likely benign ★★ same type
CADPS2 p.Glu1010Lys Benign ★★ same type
CADPS2 p.Leu154= Likely benign ★★ same type
CADPS2 p.Lys338= Benign ★★ same type
CADPS2 p.Met828Val Benign ★★ ⚠ same type
CADPS2 p.Thr819= Benign ★★ 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/caps2-p-phe429val (accessed [today's date]).

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