Is CABP2 p.Met113Ile (c.339G>A) pathogenic?

CABP2 p.Met113Ile (c.339G>A) is classified Uncertain significance in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.9611); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with CABP2 p.Met113Ile (c.339G>A)?

CABP2 p.Met113Ile (c.339G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CABP2 p.Met113Ile (c.339G>A) in the general population?

CABP2 p.Met113Ile (c.339G>A) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about CABP2 p.Met113Ile (c.339G>A)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

CABP2 p.Met113Ile

c.339G>A · rs368368611 · VCV3136247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic · top 9% in CABP2
REVEL	0.308	indeterminate
SaProt	LLR -9.96	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,814 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000342% 5/1,461,766 alleles · ultra-rare

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.Met113Ile
Coding: c.339G>A
MANE Select: NM_016366
dbSNP: rs368368611
Type: single nucleotide variant
Location: chr11:67521065 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 113: the ef-hand 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CABP2 p.Arg101Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg108Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg216Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg220Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg73Gln Uncertain significance ★★ ⚠ same condition
CABP2 p.Arg73Trp Uncertain significance ★★ ⚠ same condition
CABP2 p.Cys100Phe Uncertain significance ★★ ⚠ same condition
CABP2 p.Gly207Cys Uncertain significance ★★ ⚠ 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-met113ile (accessed [today's date]).

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