Is CAPS p.Arg47Pro (c.140G>C) pathogenic?

CAPS p.Arg47Pro (c.140G>C) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.6156); Very rare (popmax 0.00017%, nfe).

How common is CAPS p.Arg47Pro (c.140G>C) in the general population?

CAPS p.Arg47Pro (c.140G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CAPS p.Arg47Pro (c.140G>C)?

AlphaMissense predicts likely pathogenic (score 0.6156) — an in-silico prediction, not a clinical call.

CAPS p.Arg47Pro

c.140G>C · VCV4218997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6156	likely pathogenic
REVEL	0.222	benign-leaning
SaProt	LLR -18.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.082	GERP -3.5, phastCons 0.001
Regional constraint	o/e 1.06	unconstrained · MANE · 912 bp · p 0.35 · regional, not allelic
Overall
CADD	1.778	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 R133P vs ClinVar R47P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,848 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,768 alleles · very rare exomes 2/1,461,410 · genomes 0/152,358 · joint denominator

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.Arg47Pro
Coding: c.140G>C
MANE Select: NM_004058
Type: single nucleotide variant
Location: chr19:5914619 (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.Arg47Trp 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-arg47pro (accessed [today's date]).

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