Is CDH10 p.Val278Leu (c.832G>C) pathogenic?

CDH10 p.Val278Leu (c.832G>C) is classified Uncertain significance in CDH10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.1748); Ultra-rare (popmax 0.0425%, amr).

How common is CDH10 p.Val278Leu (c.832G>C) in the general population?

CDH10 p.Val278Leu (c.832G>C) is ultra-rare (popmax 0.0425%, amr) (gnomAD).

What do computational predictors say about CDH10 p.Val278Leu (c.832G>C)?

AlphaMissense predicts likely benign (score 0.1748) — an in-silico prediction, not a clinical call.

CDH10 p.Val278Leu

c.832G>C · rs928187381 · VCV3141073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1748 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0425%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1748	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -9.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.42	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 2.7, phastCons 0.99
Regional constraint	o/e 0.81	unconstrained · MANE · 46 kb · p 1.8e-06 · regional, not allelic
Overall
CADD	26.0	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 0.0425% Admixed American · 25/58,804 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0252%

Overall 0.00191% 30/1,570,506 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0425%	2,352
Remaining individualsnot grpmax-eligible	0.00494%	20,247
African / African-American	0.00276%	36,232

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: CDH10
Protein: p.Val278Leu
Coding: c.832G>C
MANE Select: NM_006727
dbSNP: rs928187381
Type: single nucleotide variant
Location: chr5:24511497 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 78.29
Residue 278: the cadherin 3 domain

Full CDH10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH10 p.Met316Ile Uncertain significance ★★ ⚠ same type
CDH10 p.Thr159Met Uncertain significance ★★ ⚠ same type
CDH10 p.Glu469= Benign ★★ same type
CDH10 p.Gly673= Benign ★★ same type
CDH10 p.Ala296Thr Uncertain significance ★ ⚠ same type
CDH10 p.Ala501Val Uncertain significance ★ ⚠ same type
CDH10 p.Ala530Val Uncertain significance ★ ⚠ same type
CDH10 p.Arg128Cys 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/cdh10-p-val278leu (accessed [today's date]).

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