Is CDH17 p.Ala269Val (c.806C>T) pathogenic?

CDH17 p.Ala269Val (c.806C>T) is classified Likely benign in CDH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1473); Rare (popmax 0.439%, afr).

How common is CDH17 p.Ala269Val (c.806C>T) in the general population?

CDH17 p.Ala269Val (c.806C>T) is rare (popmax 0.439%, afr) (gnomAD).

What do computational predictors say about CDH17 p.Ala269Val (c.806C>T)?

AlphaMissense predicts likely benign (score 0.1473) — an in-silico prediction, not a clinical call.

CDH17 p.Ala269Val

c.806C>T · rs111589116 · VCV738198

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1473 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.439%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1473	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 66 kb · p 0.44 · regional, not allelic
Overall
CADD	20.8	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 0.439% African / African-American · 329/74,984 alleles

Filtering AF 0.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.384%

Overall 0.0276% 445/1,613,646 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.439%	228
Admixed American	0.0533%	1,875
Remaining individualsnot grpmax-eligible	0.0272%	3,676
European (non-Finnish)	0.00559%	17,875
Finnishnot grpmax-eligible	0.00156%	64,004

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: CDH17
Protein: p.Ala269Val
Coding: c.806C>T
MANE Select: NM_004063
dbSNP: rs111589116
Type: single nucleotide variant
Location: chr8:94170963 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 3 PDB
Residue 269: the cadherin 3 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-ala269val (accessed [today's date]).

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