Is CAPS p.Arg84Trp (c.250C>T) pathogenic?

CAPS p.Arg84Trp (c.250C>T) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely benign (0.1138); Very rare (popmax 0.008%, afr).

How common is CAPS p.Arg84Trp (c.250C>T) in the general population?

CAPS p.Arg84Trp (c.250C>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about CAPS p.Arg84Trp (c.250C>T)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

CAPS p.Arg84Trp

c.250C>T · VCV3484911

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -11.17	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 0.4	GERP 0.46, phastCons 0.96
Overall
CADD	23.1	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 R170W vs ClinVar R84W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.008% African / African-American · 6/75,032 alleles

Filtering AF 0.00395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00416% 67/1,608,844 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,505
European (non-Finnish)	0.00501%	19,956
South Asian	0.00222%	45,110

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.Arg84Trp
Coding: c.250C>T
MANE Select: NM_003716 · reported on NM_004058
Type: single nucleotide variant
Location: chr19:5914729 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 84: the 'disordered' region

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

Similar variants

CADPS p.Ser203= Benign ★★ same type
CADPS p.Tyr579= Benign ★★ same type
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CADPS c.3477+2T>G Uncertain significance ★ same type
CADPS p.Ala1047Thr Uncertain significance ★ ⚠ same type
CADPS p.Ala1057Val Uncertain significance ★ ⚠ same type
CADPS p.Ala1114Thr 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-arg84trp (accessed [today's date]).

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