Is CAPS p.Pro88Thr (c.262C>A) pathogenic?

CAPS p.Pro88Thr (c.262C>A) is classified Benign in CAPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-26). AlphaMissense: ambiguous (0.3989); Common (popmax 7.13%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CAPS p.Pro88Thr (c.262C>A)?

AlphaMissense predicts ambiguous (score 0.3989) — an in-silico prediction, not a clinical call.

CAPS p.Pro88Thr

Q: How common is CAPS p.Pro88Thr (c.262C>A) in the general population?

CAPS p.Pro88Thr (c.262C>A) is common (popmax 7.13%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.262C>A · rs61741511 · VCV769950

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3989 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.13%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3989	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -13.81	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
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 P174T vs ClinVar P88T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.13% African / African-American · 5,344/74,992 alleles

Filtering AF 6.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.9%

Overall 0.376% 6,020/1,601,158 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.13%	14
Admixed American	0.462%	216
Remaining individualsnot grpmax-eligible	0.424%	236
Middle Eastern	0.144%	695
South Asian	0.0706%	1,417
European (non-Finnish)	0.00535%	18,699

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.Pro88Thr
Coding: c.262C>A
MANE Select: NM_003716 · reported on NM_004058
dbSNP: rs61741511
Type: single nucleotide variant
Location: chr19:5914940 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 88: 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
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
CADPS p.Ala256Val 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-pro88thr (accessed [today's date]).

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