Is CDH17 p.Tyr633Ser (c.1898A>C) pathogenic?

CDH17 p.Tyr633Ser (c.1898A>C) is classified Uncertain significance in CDH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: ambiguous (0.4273); Ultra-rare (popmax 0.0198%, afr).

How common is CDH17 p.Tyr633Ser (c.1898A>C) in the general population?

CDH17 p.Tyr633Ser (c.1898A>C) is ultra-rare (popmax 0.0198%, afr) (gnomAD).

What do computational predictors say about CDH17 p.Tyr633Ser (c.1898A>C)?

AlphaMissense predicts ambiguous (score 0.4273) — an in-silico prediction, not a clinical call.

CDH17 p.Tyr633Ser

c.1898A>C · VCV3998863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4273 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, afr)

Computational evidence

Protein change
AlphaMissense	0.4273	ambiguous
REVEL	0.526	indeterminate
SaProt	LLR -14.21	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 66 kb · p 0.44 · regional, not allelic
Overall
CADD	25.0	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 0.0198% African / African-American · 14/70,670 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00955%

Overall 0.000904% 14/1,548,352 alleles · ultra-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: CDH17
Protein: p.Tyr633Ser
Coding: c.1898A>C
MANE Select: NM_004063
Type: single nucleotide variant
Location: chr8:94148773 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 3 PDB
Residue 633: the cadherin 6 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-tyr633ser (accessed [today's date]).

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