Is CAPS p.Val4Met (c.10G>A) pathogenic?

CAPS p.Val4Met (c.10G>A) is classified Uncertain significance in CAPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.1802); Ultra-rare (popmax 0.0164%, mid).

How common is CAPS p.Val4Met (c.10G>A) in the general population?

CAPS p.Val4Met (c.10G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CAPS p.Val4Met (c.10G>A)?

AlphaMissense predicts likely benign (score 0.1802) — an in-silico prediction, not a clinical call.

CAPS p.Val4Met

c.10G>A · rs1453760777 · VCV3137241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1802 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1802	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -11.59	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 5.6	GERP 0.68, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 912 bp · p 0.35 · regional, not allelic
Overall
CADD	20.7	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 V90M vs ClinVar V4M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00112% 18/1,613,018 alleles · ultra-rare exomes 15/1,460,814 · genomes 3/152,204 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00668%	14,965
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00102%	98,330

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.Val4Met
Coding: c.10G>A
MANE Select: NM_004058
dbSNP: rs1453760777
Type: single nucleotide variant
Location: chr19:5914416 (GRCh38)
Gene constraint: LOEUF 1.458 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.49 · 1 PDB
Residue 90 UniProt numbering: an α-helix

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

Similar variants

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
CAPS p.Ala85Val Uncertain significance ★ ⚠ same type
CAPS p.Arg107Gly 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-val4met (accessed [today's date]).

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