Is CAPS2 p.Arg47Gln (c.140G>A) pathogenic?

CAPS2 p.Arg47Gln (c.140G>A) is classified Uncertain significance in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely benign (0.0974); Ultra-rare (popmax 0.0192%, afr).

How common is CAPS2 p.Arg47Gln (c.140G>A) in the general population?

CAPS2 p.Arg47Gln (c.140G>A) is ultra-rare (popmax 0.0192%, afr) (gnomAD).

What do computational predictors say about CAPS2 p.Arg47Gln (c.140G>A)?

AlphaMissense predicts likely benign (score 0.0974) — an in-silico prediction, not a clinical call.

CAPS2 p.Arg47Gln

c.140G>A · VCV3995331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0974 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0192%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0974	likely benign
REVEL	0.027	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 -1.3	GERP 0.49
Overall
CADD	17.1	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 R66Q vs ClinVar R47Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0192% African / African-American · 14/72,854 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00928%

Overall 0.0024% 37/1,543,728 alleles · ultra-rare exomes 28/1,391,644 · genomes 9/152,084 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0192%	5,204
Admixed American	0.0059%	16,937
Remaining individualsnot grpmax-eligible	0.00503%	19,876
European (non-Finnish)	0.00149%	67,265

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.Arg47Gln
Coding: c.140G>A
MANE Select: NM_001355024
Type: single nucleotide variant
Location: chr12:75323214 (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-arg47gln (accessed [today's date]).

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