Is CABP2 p.Leu157Pro (c.470T>C) pathogenic?

CABP2 p.Leu157Pro (c.470T>C) is classified Uncertain significance in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-12). AlphaMissense: likely pathogenic (0.9951); Very rare (popmax 0.0022%, sas); Associated with hearing loss disorder.

What condition is associated with CABP2 p.Leu157Pro (c.470T>C)?

CABP2 p.Leu157Pro (c.470T>C) is associated with hearing loss disorder (ClinVar).

How common is CABP2 p.Leu157Pro (c.470T>C) in the general population?

CABP2 p.Leu157Pro (c.470T>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CABP2 p.Leu157Pro (c.470T>C)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

CABP2 p.Leu157Pro

c.470T>C · rs1349245853 · VCV1065012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hearing loss disorder

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 1% in CABP2
REVEL	0.896	moderately pathogenic-leaning
SaProt	LLR -15.83	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000372% 6/1,613,028 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,542
European (non-Finnish)	0.000339%	294,961

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.Leu157Pro
Coding: c.470T>C
MANE Select: NM_016366
dbSNP: rs1349245853
Type: single nucleotide variant
Location: chr11:67520070 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 157: 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

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

Similar variants

CABP2 c.637+1G>T Pathogenic/Likely pathogenic ★★ same type
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
CABP2 p.Arg220Gln Uncertain significance ★★ ⚠ same type
CABP2 p.Arg73Gln 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-leu157pro (accessed [today's date]).

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