Is CABP4 p.Ala229Val (c.686C>T) pathogenic?

CABP4 p.Ala229Val (c.686C>T) is classified Uncertain significance in CABP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-23). AlphaMissense: likely benign (0.1584); Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with CABP4 p.Ala229Val (c.686C>T)?

CABP4 p.Ala229Val (c.686C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CABP4 p.Ala229Val (c.686C>T) in the general population?

CABP4 p.Ala229Val (c.686C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CABP4 p.Ala229Val (c.686C>T)?

AlphaMissense predicts likely benign (score 0.1584) — an in-silico prediction, not a clinical call.

CABP4 p.Ala229Val

c.686C>T · rs769011802 · VCV971754

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1584 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1584	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -10.20	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 0.69	GERP 1.1, phastCons 0.28
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	20.3	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 0.0166% Middle Eastern · 1/6,042 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000992% 16/1,613,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,042
African / African-American	0.00801%	12,483
Remaining individualsnot grpmax-eligible	0.0048%	20,820
European (non-Finnish)	0.000509%	196,573

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.Ala229Val
Coding: c.686C>T
MANE Select: NM_145200
dbSNP: rs769011802
Type: single nucleotide variant
Location: chr11:67458405 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 229: the ef-hand 3 domain

Full CABP4 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

CABP4 p.Ala229Thr Uncertain significance ★ ⚠ same residue
CABP4 p.Ala229= Likely benign ★ same residue
CABP4 p.Ala107Thr Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala108Thr Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala137Thr Uncertain significance ★★ same condition
CABP4 p.Ala203Val Uncertain significance ★★ ⚠ same condition
CABP4 p.Ala234Val Uncertain significance ★★ ⚠ same condition
CABP4 p.Arg152Trp 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/cabp4-p-ala229val (accessed [today's date]).

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