Is CABP2 p.Val85Phe (c.253G>T) pathogenic?

CABP2 p.Val85Phe (c.253G>T) is classified Uncertain significance in CABP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.1424); Ultra-rare (popmax 0.022%, sas).

How common is CABP2 p.Val85Phe (c.253G>T) in the general population?

CABP2 p.Val85Phe (c.253G>T) is ultra-rare (popmax 0.022%, sas) (gnomAD).

What do computational predictors say about CABP2 p.Val85Phe (c.253G>T)?

AlphaMissense predicts likely benign (score 0.1424) — an in-silico prediction, not a clinical call.

CABP2 p.Val85Phe

c.253G>T · VCV3342672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1424 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1424	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.74	GERP -0.87, phastCons 0.21
Regional constraint	o/e 0.99	unconstrained · MANE · 4,184 bp · p 0.9 · regional, not allelic
Overall
CADD	20.8	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 0.022% South Asian · 20/91,072 alleles

Filtering AF 0.0145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00171% 25/1,460,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.022%	4,554
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.000169%	589,981

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.Val85Phe
Coding: c.253G>T
MANE Select: NM_016366
Type: single nucleotide variant
Location: chr11:67521151 (GRCh38)
Gene constraint: LOEUF 1.299 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.93
Residue 85: the ef-hand 1 domain

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

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-val85phe (accessed [today's date]).

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