Is CDH3 p.Asp108His (c.322G>C) pathogenic?

CDH3 p.Asp108His (c.322G>C) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). AlphaMissense: likely benign (0.3111); Very rare (popmax 0.00266%, afr).

How common is CDH3 p.Asp108His (c.322G>C) in the general population?

CDH3 p.Asp108His (c.322G>C) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about CDH3 p.Asp108His (c.322G>C)?

AlphaMissense predicts likely benign (score 0.3111) — an in-silico prediction, not a clinical call.

CDH3 p.Asp108His

c.322G>C · rs2152099845 · VCV1475114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3111	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; 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	28.2	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 0.00266% African / African-American · 2/75,048 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000137% 2/1,461,462 alleles · very rare

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.Asp108His
Coding: c.322G>C
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs2152099845
Type: single nucleotide variant
Location: chr16:68678209 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 108: the cadherin 1 domain

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

Similar variants

CDH3 p.Asp108= Conflicting classifications of pathogenicity ★ same residue
CDH15 p.Ala108= Likely benign ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ same type
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
CDH3 p.Gln299Ter Pathogenic ★★ 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/cdh3-p-asp108his (accessed [today's date]).

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