Is CABP2 p.Arg63Gln (c.188G>A) pathogenic?

CABP2 p.Arg63Gln (c.188G>A) is classified Benign/Likely benign in CABP2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.2096); Rare (popmax 0.615%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 93.

What condition is associated with CABP2 p.Arg63Gln (c.188G>A)?

CABP2 p.Arg63Gln (c.188G>A) is associated with autosomal recessive nonsyndromic hearing loss 93 (ClinVar).

How common is CABP2 p.Arg63Gln (c.188G>A) in the general population?

CABP2 p.Arg63Gln (c.188G>A) is rare (popmax 0.615%, nfe) (gnomAD).

What do computational predictors say about CABP2 p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.2096) — an in-silico prediction, not a clinical call.

CABP2 p.Arg63Gln

c.188G>A · rs149431491 · VCV449907

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.2096 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.615%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 93

Computational evidence

Protein change
AlphaMissense	0.2096	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.63	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 3.1	GERP 0.63, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	23.4	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 0.615% European (non-Finnish) · 7,072/1,149,606 alleles

Filtering AF 0.603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.598%

Overall 0.548% 8,534/1,556,344 alleles · rare exomes 7,938/1,404,022 · genomes 596/152,322 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.19%	46
Ashkenazi Jewishnot grpmax-eligible	0.715%	140
European (non-Finnish)grpmax	0.615%	163
Remaining individualsnot grpmax-eligible	0.518%	193
Finnishnot grpmax-eligible	0.517%	193
Middle Eastern	0.418%	239
South Asian	0.335%	298
East Asian	0.305%	328
Admixed American	0.206%	485
African / African-American	0.0994%	1,006

Amish 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.Arg63Gln
Coding: c.188G>A
MANE Select: NM_016366
dbSNP: rs149431491
Type: single nucleotide variant
Location: chr11:67522571 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93

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.Arg63Gly Uncertain significance ★ 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.Arg94Gln 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-arg63gln (accessed [today's date]).

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