Is CABP2 p.Pro43Ser (c.127C>T) pathogenic?

CABP2 p.Pro43Ser (c.127C>T) is classified Uncertain significance in CABP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0703); Ultra-rare (popmax 0.0346%, sas); Associated with autosomal recessive nonsyndromic hearing loss 93.

What condition is associated with CABP2 p.Pro43Ser (c.127C>T)?

CABP2 p.Pro43Ser (c.127C>T) is associated with autosomal recessive nonsyndromic hearing loss 93 (ClinVar).

How common is CABP2 p.Pro43Ser (c.127C>T) in the general population?

CABP2 p.Pro43Ser (c.127C>T) is ultra-rare (popmax 0.0346%, sas) (gnomAD).

What do computational predictors say about CABP2 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

CABP2 p.Pro43Ser

c.127C>T · rs753393128 · VCV2671675

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 93

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.67	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 1.2	GERP -1.3, phastCons 0.053
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	5.573	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0346% South Asian · 29/83,892 alleles

Filtering AF 0.0247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00279% 39/1,396,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0346%	2,893
Remaining individualsnot grpmax-eligible	0.005%	19,999
European (non-Finnish)	0.000611%	163,679

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_016366
dbSNP: rs753393128
Type: single nucleotide variant
Location: chr11:67522632 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 43: 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.Met1Ile 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-pro43ser (accessed [today's date]).

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