Is CABP4 p.Val25Ile (c.73G>A) pathogenic?

CABP4 p.Val25Ile (c.73G>A) is classified Uncertain significance in CABP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-17). AlphaMissense: likely benign (0.0808); Absent from gnomAD v4.1.

How common is CABP4 p.Val25Ile (c.73G>A) in the general population?

CABP4 p.Val25Ile (c.73G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CABP4 p.Val25Ile (c.73G>A)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

CABP4 p.Val25Ile

c.73G>A · rs1455035481 · VCV2009714

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -7.45	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 3.8	GERP 0.46, phastCons 0.99
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	9.647	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CABP4
Protein: p.Val25Ile
Coding: c.73G>A
MANE Select: NM_145200
dbSNP: rs1455035481
Type: single nucleotide variant
Location: chr11:67455496 (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.Val25Ala 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-val25ile (accessed [today's date]).

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