Is CABP4 p.Val25Ala (c.74T>C) pathogenic?

CABP4 p.Val25Ala (c.74T>C) is classified Uncertain significance in CABP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely benign (0.0665); Very rare (popmax 8.49e-05%, nfe).

How common is CABP4 p.Val25Ala (c.74T>C) in the general population?

CABP4 p.Val25Ala (c.74T>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CABP4 p.Val25Ala (c.74T>C)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

CABP4 p.Val25Ala

c.74T>C · rs2135171897 · VCV1443543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -4.99	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 -5	GERP -3.2
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	0.007	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,760 alleles

Overall 6.87e-05% 1/1,455,064 alleles · very rare

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: CABP4
Protein: p.Val25Ala
Coding: c.74T>C
MANE Select: NM_145200
dbSNP: rs2135171897
Type: single nucleotide variant
Location: chr11:67455497 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 25: the 'disordered' region

Full CABP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABP4 p.Val25Ile Uncertain significance ★★ ⚠ same residue
CABP4 p.Val25Phe Uncertain significance ★ ⚠ same residue
CABP4 c.366+1G>T Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg216Ter Pathogenic ★★ same type
CABP4 p.Arg225Ter Pathogenic ★★ same type
CABP4 p.Arg49Ter Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg52Ter Pathogenic ★★ 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/cabp4-p-val25ala (accessed [today's date]).

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