Is CDH17 p.Asp428Ala (c.1283A>C) pathogenic?

CDH17 p.Asp428Ala (c.1283A>C) is classified Uncertain significance in CDH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0906); Absent from gnomAD v4.1.

How common is CDH17 p.Asp428Ala (c.1283A>C) in the general population?

CDH17 p.Asp428Ala (c.1283A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH17 p.Asp428Ala (c.1283A>C)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

CDH17 p.Asp428Ala

c.1283A>C · VCV4651071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,094)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 66 kb · p 0.44 · regional, not allelic
Overall
CADD	13.84	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

No allele count reported in gnomAD v4.1 (AN 1,594,094). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH17
Protein: p.Asp428Ala
Coding: c.1283A>C
MANE Select: NM_004063
Type: single nucleotide variant
Location: chr8:94162162 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 3 PDB
Residue 428: the cadherin 4 domain

Full CDH17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH17 p.Leu362Arg Uncertain significance ★★ ⚠ same type
CDH17 p.Ala788= Benign/Likely benign ★★ same type
CDH17 p.Arg499His Benign ★★ same type
CDH17 p.Glu739Ala Benign ★★ ⚠ same type
CDH17 c.1796+2T>C Uncertain significance ★ same type
CDH17 p.Ala101Ser Uncertain significance ★ ⚠ same type
CDH17 p.Ala157Thr Uncertain significance ★ ⚠ same type
CDH17 p.Ala241Ser 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/cdh17-p-asp428ala (accessed [today's date]).

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