Is CABP4 p.Ala244Val (c.731C>T) pathogenic?

CABP4 p.Ala244Val (c.731C>T) is classified Conflicting classifications of pathogenicity in CABP4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-16). AlphaMissense: likely benign (0.0926); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with CABP4 p.Ala244Val (c.731C>T)?

CABP4 p.Ala244Val (c.731C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CABP4 p.Ala244Val (c.731C>T) in the general population?

CABP4 p.Ala244Val (c.731C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CABP4 p.Ala244Val (c.731C>T)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

CABP4 p.Ala244Val

c.731C>T · rs569810738 · VCV1013970

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -9.83	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 -2.4	GERP -4.6
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	10.91	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 0.0178% East Asian · 8/44,872 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00607% 98/1,613,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,609
Middle Eastern	0.0165%	6,058
European (non-Finnish)	0.00686%	14,567
Admixed American	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00267%	37,485
Finnishnot grpmax-eligible	0.00156%	63,980
South Asian	0.0011%	91,070

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.Ala244Val
Coding: c.731C>T
MANE Select: NM_145200
dbSNP: rs569810738
Type: single nucleotide variant
Location: chr11:67458450 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 244: the ef-hand 4 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.Ala244= 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.Ala229Val 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-ala244val (accessed [today's date]).

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