Is CABP4 p.Arg152Trp (c.454C>T) pathogenic?

CABP4 p.Arg152Trp (c.454C>T) is classified Uncertain significance in CABP4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-17). AlphaMissense: likely benign (0.2396); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with CABP4 p.Arg152Trp (c.454C>T)?

CABP4 p.Arg152Trp (c.454C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CABP4 p.Arg152Trp (c.454C>T) in the general population?

CABP4 p.Arg152Trp (c.454C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CABP4 p.Arg152Trp (c.454C>T)?

AlphaMissense predicts likely benign (score 0.2396) — an in-silico prediction, not a clinical call.

CABP4 p.Arg152Trp

c.454C>T · rs756392923 · VCV2965111

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2396 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2396	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -12.54	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.091, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	27.6	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00105% 17/1,613,636 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00329%	30,363
African / African-American	0.00267%	37,451
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000847%	118,002

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.Arg152Trp
Coding: c.454C>T
MANE Select: NM_145200
dbSNP: rs756392923
Type: single nucleotide variant
Location: chr11:67456355 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 152: the ef-hand 1 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.Arg152Gln Benign/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.Arg159Gln 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-arg152trp (accessed [today's date]).

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