Is CABP4 p.Arg124Cys (c.370C>T) pathogenic?

CABP4 p.Arg124Cys (c.370C>T) is classified Conflicting classifications of pathogenicity in CABP4 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-18). AlphaMissense: likely pathogenic (0.5671); Ultra-rare (popmax 0.0397%, nfe); Associated with CABP4-related disorder.

What condition is associated with CABP4 p.Arg124Cys (c.370C>T)?

CABP4 p.Arg124Cys (c.370C>T) is associated with CABP4-related disorder, cone-rod synaptic disorder, congenital nonprogressive (ClinVar).

How common is CABP4 p.Arg124Cys (c.370C>T) in the general population?

CABP4 p.Arg124Cys (c.370C>T) is ultra-rare (popmax 0.0397%, nfe) (gnomAD).

What do computational predictors say about CABP4 p.Arg124Cys (c.370C>T)?

AlphaMissense predicts likely pathogenic (score 0.5671) — an in-silico prediction, not a clinical call.

CABP4 p.Arg124Cys

c.370C>T · rs121917828 · VCV1953

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5671 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0397%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CABP4-related disorder

Computational evidence

Protein change
AlphaMissense	0.5671	likely pathogenic
REVEL	0.372	indeterminate
SaProt	LLR -12.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	25.4	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 0.0397% European (non-Finnish) · 469/1,179,894 alleles

Filtering AF 0.0367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0355%

Overall 0.031% 500/1,613,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0397%	2,516
African / African-American	0.0293%	3,410
Remaining individualsnot grpmax-eligible	0.0096%	10,415
East Asian	0.00446%	22,415
Finnishnot grpmax-eligible	0.00158%	63,322

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.Arg124Cys
Coding: c.370C>T
MANE Select: NM_145200
dbSNP: rs121917828
Type: single nucleotide variant
Location: chr11:67456191 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.01
Residue 124: a UniProt-annotated variant site (in crsd)

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

Disease context

CABP4-related disorder

Also linked: cone-rod synaptic disorder, congenital nonprogressive

Similar variants

CABP4 p.Arg124fs Pathogenic/Likely pathogenic ★★ same residue
CABP4 p.Arg124= Likely benign ★★ same residue
CABP4 p.Arg124His Conflicting classifications of pathogenicity ★ same residue
CABP4 p.Arg124Leu Uncertain significance ★ ⚠ same residue
CABP4 c.366+1G>T Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
CABP4 p.Arg216Ter Pathogenic ★★ same condition
CABP4 p.Arg225Ter 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-arg124cys (accessed [today's date]).

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