Is CAPS p.Ala43Thr (c.127G>A) pathogenic?

CAPS p.Ala43Thr (c.127G>A) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely benign (0.0795); Ultra-rare (popmax 0.0495%, mid).

How common is CAPS p.Ala43Thr (c.127G>A) in the general population?

CAPS p.Ala43Thr (c.127G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CAPS p.Ala43Thr (c.127G>A)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

CAPS p.Ala43Thr

c.127G>A · rs749944148 · VCV2382169

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP -3.5, phastCons 0.89
Overall
CADD	16.72	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 and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A129T vs ClinVar A43T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0242% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.0126% 204/1,613,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
African / African-American	0.0346%	2,887
European (non-Finnish)	0.0141%	7,106
Remaining individualsnot grpmax-eligible	0.0112%	8,924
Admixed American	0.00333%	29,992

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.Ala43Thr
Coding: c.127G>A
MANE Select: NM_003716 · reported on NM_004058
dbSNP: rs749944148
Type: single nucleotide variant
Location: chr19:5914606 (GRCh38)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 43: the 'disordered' region

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

Similar variants

CADPS p.Ala43Val Uncertain significance ★ ⚠ same residue
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

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-ala43thr (accessed [today's date]).

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