Is CAPS2 p.Val105Ile (c.313G>A) pathogenic?

CAPS2 p.Val105Ile (c.313G>A) is classified Likely benign in CAPS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.00428%, nfe).

How common is CAPS2 p.Val105Ile (c.313G>A) in the general population?

CAPS2 p.Val105Ile (c.313G>A) is very rare (popmax 0.00428%, nfe) (gnomAD).

What do computational predictors say about CAPS2 p.Val105Ile (c.313G>A)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

CAPS2 p.Val105Ile

c.313G>A · rs923328818 · VCV2373767

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00428%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -0.93
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V162I vs ClinVar V105I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00428% European (non-Finnish) · 49/1,144,146 alleles

Filtering AF 0.00328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00329% 51/1,547,904 alleles · very rare exomes 51/1,395,828 · genomes 0/152,076 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00428%	23,350
African / African-American	0.00274%	36,502

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: CAPS2
Protein: p.Val105Ile
Coding: c.313G>A
MANE Select: NM_001355024
dbSNP: rs923328818
Type: single nucleotide variant
Location: chr12:75321441 (GRCh38)
Gene constraint: LOEUF 1.457 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.30

Full CAPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPS2 p.Glu189= Benign ★★ same type
CAPS2 p.Ser52= Benign ★★ same type
CAPS2 c.1281+1G>C Uncertain significance ★ same type
CAPS2 c.177+130C>A Uncertain significance ★ ⚠ same type
CAPS2 c.177+142C>T Uncertain significance ★ ⚠ same type
CAPS2 c.177+156G>T Uncertain significance ★ ⚠ same type
CAPS2 c.354+1G>T Uncertain significance ★ same type
CAPS2 c.-1A>T 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/caps2-p-val105ile (accessed [today's date]).

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