Is CDH3 p.Ala361Ser (c.1081G>T) pathogenic?

CDH3 p.Ala361Ser (c.1081G>T) is classified Uncertain significance in CDH3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-06-12). AlphaMissense: likely benign (0.1002); Very rare (popmax 0.00347%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH3 p.Ala361Ser (c.1081G>T)?

CDH3 p.Ala361Ser (c.1081G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH3 p.Ala361Ser (c.1081G>T) in the general population?

CDH3 p.Ala361Ser (c.1081G>T) is very rare (popmax 0.00347%, nfe) (gnomAD).

What do computational predictors say about CDH3 p.Ala361Ser (c.1081G>T)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

CDH3 p.Ala361Ser

c.1081G>T · rs757205517 · VCV290054

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00347%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	23.8	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 0.00347% European (non-Finnish) · 41/1,180,028 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00273% 44/1,613,966 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00347%	28,781
African / African-American	0.00267%	37,469
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ala361Ser
Coding: c.1081G>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs757205517
Type: single nucleotide variant
Location: chr16:68682386 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 361: the cadherin 3 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH3 p.Ala361Val Uncertain significance ★★ ⚠ same residue
CDH3 p.Ala361= Likely benign ★★ same residue
CDH3 p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala22Glu Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala356Pro Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala64Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala724Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala749Ser Uncertain significance ★★ ⚠ 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-ala361ser (accessed [today's date]).

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