Is CAPS2 p.Asp264Tyr (c.790G>T) pathogenic?

CAPS2 p.Asp264Tyr (c.790G>T) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely pathogenic (0.7344); Ultra-rare (popmax 0.0561%, afr).

How common is CAPS2 p.Asp264Tyr (c.790G>T) in the general population?

CAPS2 p.Asp264Tyr (c.790G>T) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

What do computational predictors say about CAPS2 p.Asp264Tyr (c.790G>T)?

AlphaMissense predicts likely pathogenic (score 0.7344) — an in-silico prediction, not a clinical call.

CAPS2 p.Asp264Tyr

c.790G>T · rs150531753 · VCV2236301

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7344 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Computational evidence

Protein change
AlphaMissense	0.7344	likely pathogenic
REVEL	0.434	indeterminate
Splicing
SpliceAI	Δ0.28	donor loss, 46 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 1.5, phastCons 0.97
Overall
CADD	23.5	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 D321Y vs ClinVar D264Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0561% African / African-American · 42/74,810 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00286% 46/1,610,836 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,781
Remaining individualsnot grpmax-eligible	0.00642%	15,580

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.Asp264Tyr
Coding: c.790G>T
MANE Select: NM_017954 · reported on NM_001355024
dbSNP: rs150531753
Type: single nucleotide variant
Location: chr12:75298917 (GRCh38)
Structure: AlphaFold pLDDT 79.91

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

Similar variants

RNF148 p.Thr264Ile Likely benign ★ 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-asp264tyr (accessed [today's date]).

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