Is CDH16 p.Pro109Leu (c.326C>T) pathogenic?

CDH16 p.Pro109Leu (c.326C>T) is classified Uncertain significance in CDH16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.111); Absent from gnomAD v4.1.

How common is CDH16 p.Pro109Leu (c.326C>T) in the general population?

CDH16 p.Pro109Leu (c.326C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH16 p.Pro109Leu (c.326C>T)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

CDH16 p.Pro109Leu

c.326C>T · VCV3488777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.309	indeterminate
SaProt	LLR -14.92	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 9.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,670 bp · p 0.11 · regional, not allelic
Overall
CADD	24.7	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: CDH16
Protein: p.Pro109Leu
Coding: c.326C>T
MANE Select: NM_004062
Type: single nucleotide variant
Location: chr16:66916163 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.17
Residue 109: the cadherin 1 domain

Full CDH16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH16 p.Arg717His Benign ★★ same type
CDH16 p.Leu377= Benign ★★ same type
CDH16 p.Ala133Ser Uncertain significance ★ ⚠ same type
CDH16 p.Ala159Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala173Thr Uncertain significance ★ ⚠ same type
CDH16 p.Ala202Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala20Thr Uncertain significance ★ ⚠ same type
CDH16 p.Ala23Thr 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/cdh16-p-pro109leu (accessed [today's date]).

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