Is CABP2 p.Val45Ile (c.133G>A) pathogenic?

CABP2 p.Val45Ile (c.133G>A) is classified Likely benign in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.0641); Ultra-rare (popmax 0.0196%, eas); Associated with Inborn genetic diseases.

What condition is associated with CABP2 p.Val45Ile (c.133G>A)?

CABP2 p.Val45Ile (c.133G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CABP2 p.Val45Ile (c.133G>A) in the general population?

CABP2 p.Val45Ile (c.133G>A) is ultra-rare (popmax 0.0196%, eas) (gnomAD).

What do computational predictors say about CABP2 p.Val45Ile (c.133G>A)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

CABP2 p.Val45Ile

c.133G>A · VCV3262652

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -7.06	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	GERP -3.2
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	0.111	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0196% East Asian · 8/40,876 alleles

Filtering AF 0.00968% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00705%

Overall 0.0051% 79/1,549,090 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0196%	5,109
African / African-American	0.00957%	10,447
Admixed American	0.00786%	12,728
Remaining individualsnot grpmax-eligible	0.00666%	15,006
European (non-Finnish)	0.00471%	21,227
Finnishnot grpmax-eligible	0.0034%	29,412

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: CABP2
Protein: p.Val45Ile
Coding: c.133G>A
MANE Select: NM_016366
Type: single nucleotide variant
Location: chr11:67522626 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 45: the 'disordered' region

Full CABP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CABP2 p.Arg101Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg108Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg216Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg73Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg73Trp Uncertain significance ★★ ⚠ same condition
CABP2 p.Cys100Phe Uncertain significance ★★ ⚠ same condition
CABP2 p.Gly207Cys Uncertain significance ★★ ⚠ same condition

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/cabp2-p-val45ile (accessed [today's date]).

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