Is CABP4 p.Leu231Pro (c.692T>C) pathogenic?

CABP4 p.Leu231Pro (c.692T>C) is classified Pathogenic/Likely pathogenic in CABP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-16). AlphaMissense: likely pathogenic (0.9779); Very rare (popmax 0.00333%, amr); Associated with CABP4-related disorder.

What condition is associated with CABP4 p.Leu231Pro (c.692T>C)?

CABP4 p.Leu231Pro (c.692T>C) is associated with CABP4-related disorder (ClinVar).

How common is CABP4 p.Leu231Pro (c.692T>C) in the general population?

CABP4 p.Leu231Pro (c.692T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CABP4 p.Leu231Pro (c.692T>C)?

AlphaMissense predicts likely pathogenic (score 0.9779) — an in-silico prediction, not a clinical call.

CABP4 p.Leu231Pro

c.692T>C · rs373308879 · VCV1007462

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9779 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CABP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.9779	likely pathogenic ✓ concordant with ClinVar · top 2% in CABP4
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -14.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	26.8	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 0.00333% Admixed American · 2/60,016 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00116% 17/1,461,308 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,008
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)	0.00119%	84,262

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.Leu231Pro
Coding: c.692T>C
MANE Select: NM_145200
dbSNP: rs373308879
Type: single nucleotide variant
Location: chr11:67458411 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 231: the ef-hand 3 domain

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

Disease context

CABP4-related disorder

Similar variants

CABP4 c.366+1G>T Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg216Ter Pathogenic ★★ same condition
CABP4 p.Arg225Ter Pathogenic ★★ same condition
CABP4 p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg52Ter Pathogenic ★★ same condition
CABP4 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Glu139Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 c.652-1G>A Likely pathogenic ★ 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-leu231pro (accessed [today's date]).

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