Is CABP2 p.Phe161fs (c.482del) pathogenic?

CABP2 p.Phe161fs (c.482del) is classified Likely pathogenic in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). Ultra-rare (popmax 0.016%, afr); Associated with autosomal recessive nonsyndromic hearing loss 93.

What condition is associated with CABP2 p.Phe161fs (c.482del)?

CABP2 p.Phe161fs (c.482del) is associated with autosomal recessive nonsyndromic hearing loss 93 (ClinVar).

How common is CABP2 p.Phe161fs (c.482del) in the general population?

CABP2 p.Phe161fs (c.482del) is ultra-rare (popmax 0.016%, afr) (gnomAD).

CABP2 p.Phe161fs

c.482del · rs368437370 · VCV1324001

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

autosomal recessive nonsyndromic hearing loss 93

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP -0.36, phastCons 1
Overall
CADD	34.0	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 0.016% African / African-American · 12/74,922 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000806% 13/1,612,188 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,243
European (non-Finnish)	8.48e-05%	1,179,686

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.Phe161fs
Coding: c.482del
MANE Select: NM_016366
dbSNP: rs368437370
Type: Deletion
Location: chr11:67520058 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 161: a UniProt-annotated variant site (in dfnb93); the ef-hand 3 domain

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 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 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-phe161fs (accessed [today's date]).

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