Is CABP2 p.Arg92Ter (c.274C>T) pathogenic?

CABP2 p.Arg92Ter (c.274C>T) is classified Pathogenic in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). Very rare (popmax 0.00134%, afr); Associated with hearing loss, autosomal recessive.

What condition is associated with CABP2 p.Arg92Ter (c.274C>T)?

CABP2 p.Arg92Ter (c.274C>T) is associated with hearing loss, autosomal recessive (ClinVar).

How common is CABP2 p.Arg92Ter (c.274C>T) in the general population?

CABP2 p.Arg92Ter (c.274C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Rare non-syndromic genetic deafness inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CABP2 p.Arg92Ter

c.274C>T · VCV3340148

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hearing loss, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.07	GERP -2, phastCons 0.001
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,856 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,613,112 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,856
South Asian	0.0011%	91,070
European (non-Finnish)	0.000424%	235,999

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.Arg92Ter
Coding: c.274C>T
MANE Select: NM_016366
Type: single nucleotide variant
Location: chr11:67521130 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 92: the ef-hand 1 domain

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

Disease context

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

For Rare non-syndromic genetic deafness (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CABP2 p.Arg92Gln Uncertain significance ★ ⚠ same residue
CABP2 p.Arg92= Likely benign ★ same residue
CABP2 c.637+1G>T Pathogenic/Likely pathogenic ★★ same condition
CABP2 p.Ala183Thr Uncertain significance ★★ ⚠ same type
CABP2 p.Arg101Gln Uncertain significance ★★ ⚠ same type
CABP2 p.Arg108Gln Uncertain significance ★★ ⚠ same type
CABP2 p.Arg11Gln Uncertain significance ★★ ⚠ same type
CABP2 p.Arg216Gln Uncertain significance ★★ ⚠ 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/cabp2-p-arg92ter (accessed [today's date]).

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