Is CABP4 p.Arg232Gln (c.695G>A) pathogenic?

CABP4 p.Arg232Gln (c.695G>A) is classified Uncertain significance in CABP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-30). AlphaMissense: likely benign (0.0936); Ultra-rare (popmax 0.0166%, mid).

How common is CABP4 p.Arg232Gln (c.695G>A) in the general population?

CABP4 p.Arg232Gln (c.695G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about CABP4 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0936) — an in-silico prediction, not a clinical call.

CABP4 p.Arg232Gln

c.695G>A · rs896656946 · VCV1473112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0936 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0936	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -10.19	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 1.2	GERP -1.2, phastCons 0.087
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	21.1	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 · 1/6,040 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000821% 12/1,461,374 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,040
East Asian	0.00223%	44,866
African / African-American	0.00133%	75,032
South Asian	0.0011%	91,064
European (non-Finnish)	0.000678%	147,467

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.Arg232Gln
Coding: c.695G>A
MANE Select: NM_145200
dbSNP: rs896656946
Type: single nucleotide variant
Location: chr11:67458414 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 232: the ef-hand 3 domain

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

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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-arg232gln (accessed [today's date]).

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