Is CABP4 p.Arg145Cys (c.433C>T) pathogenic?

CABP4 p.Arg145Cys (c.433C>T) is classified Uncertain significance in CABP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1104); Ultra-rare (popmax 0.015%, amr).

How common is CABP4 p.Arg145Cys (c.433C>T) in the general population?

CABP4 p.Arg145Cys (c.433C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CABP4 p.Arg145Cys (c.433C>T)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

CABP4 p.Arg145Cys

c.433C>T · rs753754780 · VCV960815

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -9.71	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 0.23	GERP 0.067, phastCons 0.007
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,008 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00105% 17/1,613,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,668
South Asian	0.0011%	91,086
European (non-Finnish)	0.000593%	168,574

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.Arg145Cys
Coding: c.433C>T
MANE Select: NM_145200
dbSNP: rs753754780
Type: single nucleotide variant
Location: chr11:67456334 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 145: the ef-hand 1 domain

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

Similar variants

CABP4 p.Arg145His Uncertain significance ★ ⚠ same residue
CABP4 c.366+1G>T Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg216Ter Pathogenic ★★ same type
CABP4 p.Arg225Ter Pathogenic ★★ same type
CABP4 p.Arg49Ter Pathogenic/Likely pathogenic ★★ same type
CABP4 p.Arg52Ter Pathogenic ★★ same type
CABP4 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same type

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-arg145cys (accessed [today's date]).

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