Is CDH26 p.Val385Met (c.1153G>A) pathogenic?

CDH26 p.Val385Met (c.1153G>A) is classified Uncertain significance in CDH26 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-31). AlphaMissense: likely benign (0.2237); Absent from gnomAD v4.1.

How common is CDH26 p.Val385Met (c.1153G>A) in the general population?

CDH26 p.Val385Met (c.1153G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH26 p.Val385Met (c.1153G>A)?

AlphaMissense predicts likely benign (score 0.2237) — an in-silico prediction, not a clinical call.

CDH26 p.Val385Met

c.1153G>A · VCV3265292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2237 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2237	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -11.64	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.45	donor gain · deltas
Pangolin	Δ0.37	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.18	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 54 kb · p 0.44 · regional, not allelic
Overall
CADD	19.61	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH26
Protein: p.Val385Met
Coding: c.1153G>A
MANE Select: NM_177980
Type: single nucleotide variant
Location: chr20:59989033 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.84
Residue 385: the cadherin 3 domain

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

Similar variants

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
CDH26 p.Ala617Pro 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-val385met (accessed [today's date]).

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