Is CDH3 p.Val205Met (c.613G>A) pathogenic?

CDH3 p.Val205Met (c.613G>A) is classified Likely pathogenic in CDH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-16). AlphaMissense: likely pathogenic (0.9201); Very rare (popmax 0.00223%, eas); Associated with CDH3-related disorder.

What condition is associated with CDH3 p.Val205Met (c.613G>A)?

CDH3 p.Val205Met (c.613G>A) is associated with CDH3-related disorder (ClinVar).

How common is CDH3 p.Val205Met (c.613G>A) in the general population?

CDH3 p.Val205Met (c.613G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CDH3 p.Val205Met (c.613G>A)?

AlphaMissense predicts likely pathogenic (score 0.9201) — an in-silico prediction, not a clinical call.

CDH3 p.Val205Met

c.613G>A · rs777186958 · VCV2137841

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CDH3-related disorder

Computational evidence

Protein change
AlphaMissense	0.9201	likely pathogenic ✓ concordant with ClinVar · top 8% in CDH3
REVEL	0.568	indeterminate
SaProt	LLR -13.75	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Overall
CADD	32.0	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 0.00223% East Asian · 1/44,890 alleles

Overall 0.000124% 2/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
Admixed American	0.00167%	60,000

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: CDH3
Protein: p.Val205Met
Coding: c.613G>A
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs777186958
Type: single nucleotide variant
Location: chr16:68678828 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 205: the cadherin 2 domain

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDH3-related disorder

Similar variants

CDH15 p.Asp205= Benign ★★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same condition
CDH3 p.Arg103Ter Pathogenic ★★ same condition
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDH3 p.Met269Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Glu289Ter Likely pathogenic ★ same condition
CDH15 p.Ala174Ser Uncertain significance ★ ⚠ same condition
CDH15 p.Arg36Gln Conflicting classifications of pathogenicity ★ ⚠ 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/cdh3-p-val205met (accessed [today's date]).

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