Is CABP2 p.Met1Ile (c.3G>A) pathogenic?

CABP2 p.Met1Ile (c.3G>A) is classified Uncertain significance in CABP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-27). Very rare (popmax 0.00758%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 93.

What condition is associated with CABP2 p.Met1Ile (c.3G>A)?

CABP2 p.Met1Ile (c.3G>A) is associated with autosomal recessive nonsyndromic hearing loss 93 (ClinVar).

How common is CABP2 p.Met1Ile (c.3G>A) in the general population?

CABP2 p.Met1Ile (c.3G>A) is very rare (popmax 0.00758%, nfe) (gnomAD).

CABP2 p.Met1Ile

c.3G>A · rs1354716315 · VCV1303918

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00758%, nfe)

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	start-loss	predicted loss-of-function
REVEL	0.369	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.5, phastCons 1
Overall
CADD	22.9	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 0.00758% European (non-Finnish) · 87/1,148,302 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00581%

Overall 0.00573% 89/1,553,400 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00758%	13,199
Remaining individualsnot grpmax-eligible	0.00333%	30,033

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.Met1Ile
Coding: c.3G>A
MANE Select: NM_016366
dbSNP: rs1354716315
Type: single nucleotide variant
Location: chr11:67523324 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 1: the 'disordered' region

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.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
CABP2 p.Glu78Lys Pathogenic ⚠ 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-met1ile (accessed [today's date]).

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