Is CDH26 p.Val293Met (c.877G>A) pathogenic?

CDH26 p.Val293Met (c.877G>A) is classified Uncertain significance in CDH26 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.1161); Ultra-rare (popmax 0.0714%, eas).

How common is CDH26 p.Val293Met (c.877G>A) in the general population?

CDH26 p.Val293Met (c.877G>A) is ultra-rare (popmax 0.0714%, eas) (gnomAD).

What do computational predictors say about CDH26 p.Val293Met (c.877G>A)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

CDH26 p.Val293Met

c.877G>A · rs370904535 · VCV2547727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0714%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.6	GERP -3.2
Regional constraint	o/e 0.98	unconstrained · MANE · 54 kb · p 0.44 · regional, not allelic
Overall
CADD	15.08	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 0.0714% East Asian · 32/44,822 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0453%

Overall 0.00539% 87/1,613,328 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0714%	1,401
South Asian	0.0418%	2,392
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00119%	84,264

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: CDH26
Protein: p.Val293Met
Coding: c.877G>A
MANE Select: NM_177980
dbSNP: rs370904535
Type: single nucleotide variant
Location: chr20:59987492 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.84
Residue 293: the cadherin 3 domain

Full CDH26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH26 p.Val293Leu Uncertain significance ★ ⚠ same residue
CDH26 p.Ala189Gly Uncertain significance ★ ⚠ same type
CDH26 p.Ala238Thr Uncertain significance ★ ⚠ same type
CDH26 p.Ala274Glu Uncertain significance ★ ⚠ same type
CDH26 p.Ala308Ser Uncertain significance ★ ⚠ same type
CDH26 p.Ala390Thr Uncertain significance ★ ⚠ same type
CDH26 p.Ala598Gly Uncertain significance ★ ⚠ same type
CDH26 p.Ala617Asp 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/cdh26-p-val293met (accessed [today's date]).

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