Is CABP2 p.Arg94Gln (c.281G>A) pathogenic?

CABP2 p.Arg94Gln (c.281G>A) is classified Benign in CABP2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0783); Common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 93.

What condition is associated with CABP2 p.Arg94Gln (c.281G>A)?

CABP2 p.Arg94Gln (c.281G>A) is associated with autosomal recessive nonsyndromic hearing loss 93 (ClinVar).

What do computational predictors say about CABP2 p.Arg94Gln (c.281G>A)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

CABP2 p.Arg94Gln

Q: How common is CABP2 p.Arg94Gln (c.281G>A) in the general population?

CABP2 p.Arg94Gln (c.281G>A) is common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.281G>A · rs2276118 · VCV506033

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 67.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 93

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.46	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 -1.8	GERP -1.6
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	14.13	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 67.7% East Asian · 30,354/44,830 alleles

Filtering AF 67.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 66.8%

Overall 54.2% 874,351/1,612,864 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	67.7%	1
East Asiangrpmax	67.7%	1
South Asian	63.5%	2
Amishnot grpmax-eligible	57.2%	2
Middle Eastern	56.6%	2
European (non-Finnish)	56.2%	2
Remaining individualsnot grpmax-eligible	54.4%	2
Finnishnot grpmax-eligible	54.1%	2
Admixed American	38.8%	3
African / African-American	10.3%	10

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CABP2
Protein: p.Arg94Gln
Coding: c.281G>A
MANE Select: NM_016366
dbSNP: rs2276118
Type: single nucleotide variant
Location: chr11:67521123 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 94: the ef-hand 1 domain; a UniProt-annotated variant site (in)

Full CABP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 93 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CABP2 p.Arg94Gly Benign ★★ same residue
CABP2 c.637+1G>T Pathogenic/Likely pathogenic ★★ same condition
CABP2 p.Met1Ile Uncertain significance ★★ same condition
CABP2 p.Pro43Ser Uncertain significance ★★ ⚠ same condition
CABP2 p.Tyr48Ser Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg63Gln Benign/Likely benign ★★ same condition
CABP2 c.490-8C>A Likely pathogenic ★ same condition
CABP2 p.Ile197Thr Conflicting classifications of pathogenicity ★ ⚠ 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/cabp2-p-arg94gln (accessed [today's date]).

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