Is CABP4 p.Arg124His (c.371G>A) pathogenic?

CABP4 p.Arg124His (c.371G>A) is classified Conflicting classifications of pathogenicity in CABP4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-09). AlphaMissense: ambiguous (0.3754); Very rare (popmax 0.00892%, eas).

How common is CABP4 p.Arg124His (c.371G>A) in the general population?

CABP4 p.Arg124His (c.371G>A) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about CABP4 p.Arg124His (c.371G>A)?

AlphaMissense predicts ambiguous (score 0.3754) — an in-silico prediction, not a clinical call.

CABP4 p.Arg124His

c.371G>A · rs201046715 · VCV1477513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Computational evidence

Protein change
AlphaMissense	0.3754	ambiguous
REVEL	0.307	indeterminate
SaProt	LLR -11.43	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -0.097, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,232 bp · p 0.15 · regional, not allelic
Overall
CADD	25.1	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 0.00892% East Asian · 4/44,860 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000992% 16/1,613,302 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,215
African / African-American	0.004%	25,005
Remaining individualsnot grpmax-eligible	0.0032%	31,245
South Asian	0.0022%	45,542
European (non-Finnish)	0.000424%	235,987

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.Arg124His
Coding: c.371G>A
MANE Select: NM_145200
dbSNP: rs201046715
Type: single nucleotide variant
Location: chr11:67456192 (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

Similar variants

CABP4 p.Arg124= Likely benign ★★ same residue
CABP4 p.Arg124Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CABP4 p.Arg124Leu Uncertain significance ★ ⚠ same residue
CABP4 p.Arg124fs Pathogenic/Likely pathogenic ★★ 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

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-arg124his (accessed [today's date]).

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