Is CAPS2 p.Asp342His (c.1024G>C) pathogenic?

CAPS2 p.Asp342His (c.1024G>C) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: ambiguous (0.4443); Very rare (popmax 0.00669%, afr).

How common is CAPS2 p.Asp342His (c.1024G>C) in the general population?

CAPS2 p.Asp342His (c.1024G>C) is very rare (popmax 0.00669%, afr) (gnomAD).

What do computational predictors say about CAPS2 p.Asp342His (c.1024G>C)?

AlphaMissense predicts ambiguous (score 0.4443) — an in-silico prediction, not a clinical call.

CAPS2 p.Asp342His

c.1024G>C · rs375186529 · VCV2318372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

Computational evidence

Protein change
AlphaMissense	0.4443	ambiguous
REVEL	0.46	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -0.4, phastCons 1
Overall
CADD	24.2	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 D399H vs ClinVar D342H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% African / African-American · 5/74,692 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000312% 5/1,602,520 alleles · very rare

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.Asp342His
Coding: c.1024G>C
MANE Select: NM_017954 · reported on NM_001355024
dbSNP: rs375186529
Type: single nucleotide variant
Location: chr12:75293274 (GRCh38)
Structure: AlphaFold pLDDT 79.91
Residue 342: the dm10 domain

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

Similar variants

RNF133 p.Pro342Ala Uncertain significance ★ ⚠ same residue
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

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-asp342his (accessed [today's date]).

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