Is CAPS p.Arg47Trp (c.139C>T) pathogenic?

CAPS p.Arg47Trp (c.139C>T) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.098); Ultra-rare (popmax 0.0307%, afr).

How common is CAPS p.Arg47Trp (c.139C>T) in the general population?

CAPS p.Arg47Trp (c.139C>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about CAPS p.Arg47Trp (c.139C>T)?

AlphaMissense predicts likely benign (score 0.098) — an in-silico prediction, not a clinical call.

CAPS p.Arg47Trp

c.139C>T · VCV3484912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.098 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.098	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -15.68	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.73, phastCons 0.062
Regional constraint	o/e 1.06	unconstrained · MANE · 912 bp · p 0.35 · regional, not allelic
Overall
CADD	19.58	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 R133W vs ClinVar R47W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,946 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00378% 61/1,613,624 alleles · ultra-rare exomes 49/1,461,394 · genomes 12/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,259
European (non-Finnish)	0.00305%	32,774
East Asian	0.00223%	44,884
South Asian	0.0011%	91,062

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: CAPS
Protein: p.Arg47Trp
Coding: c.139C>T
MANE Select: NM_004058
Type: single nucleotide variant
Location: chr19:5914618 (GRCh38)
Gene constraint: LOEUF 1.458 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.49 · 1 PDB
Residue 133 UniProt numbering: the ef-hand 1 domain; an α-helix

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

Similar variants

CAPS p.Arg47Pro Uncertain significance ★ ⚠ same residue
CAPS p.Arg47Gln Likely benign ★ ⚠ same residue
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CAPS p.Ala13Glu Uncertain significance ★ ⚠ same type
CAPS p.Ala27Ser Uncertain significance ★ ⚠ same type
CAPS p.Ala43Thr Uncertain significance ★ ⚠ same type
CAPS p.Ala60Glu 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/caps-p-arg47trp (accessed [today's date]).

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