Is CAPS2 p.Ile63Val (c.187A>G) pathogenic?

CAPS2 p.Ile63Val (c.187A>G) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.0697); Ultra-rare (popmax 0.0147%, eas).

How common is CAPS2 p.Ile63Val (c.187A>G) in the general population?

CAPS2 p.Ile63Val (c.187A>G) is ultra-rare (popmax 0.0147%, eas) (gnomAD).

What do computational predictors say about CAPS2 p.Ile63Val (c.187A>G)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

CAPS2 p.Ile63Val

c.187A>G · rs1227216218 · VCV3137251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.1
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I120V vs ClinVar I63V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% East Asian · 6/40,744 alleles

Filtering AF 0.00637% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00436%

Overall 0.000454% 7/1,540,786 alleles · ultra-rare exomes 3/1,388,516 · genomes 4/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0147%	6,791
African / African-American	0.00138%	72,546

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.Ile63Val
Coding: c.187A>G
MANE Select: NM_001355024
dbSNP: rs1227216218
Type: single nucleotide variant
Location: chr12:75321567 (GRCh38)
Gene constraint: LOEUF 1.457 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.30

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

Similar variants

CAPS2 p.Glu189= Benign ★★ same type
CAPS2 p.Ser52= Benign ★★ same type
CAPS2 c.1281+1G>C Uncertain significance ★ same type
CAPS2 c.177+130C>A Uncertain significance ★ ⚠ same type
CAPS2 c.177+142C>T Uncertain significance ★ ⚠ same type
CAPS2 c.177+156G>T Uncertain significance ★ ⚠ same type
CAPS2 c.354+1G>T Uncertain significance ★ same type
CAPS2 c.-1A>T 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/caps2-p-ile63val (accessed [today's date]).

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