Is CDH17 p.Arg86Thr (c.257G>C) pathogenic?

CDH17 p.Arg86Thr (c.257G>C) is classified Uncertain significance in CDH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely pathogenic (0.8288); Rare (popmax 0.122%, sas).

How common is CDH17 p.Arg86Thr (c.257G>C) in the general population?

CDH17 p.Arg86Thr (c.257G>C) is rare (popmax 0.122%, sas) (gnomAD).

What do computational predictors say about CDH17 p.Arg86Thr (c.257G>C)?

AlphaMissense predicts likely pathogenic (score 0.8288) — an in-silico prediction, not a clinical call.

CDH17 p.Arg86Thr

c.257G>C · rs762951650 · VCV2344256

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8288 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.122%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8288	likely pathogenic · top 9% in CDH17
REVEL	0.377	indeterminate
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 66 kb · p 0.44 · regional, not allelic
Overall
CADD	21.8	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 0.122% South Asian · 111/91,046 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0965%

Overall 0.0112% 180/1,613,796 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.122%	820
Middle Eastern	0.0826%	1,211
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00458%	21,848
Admixed American	0.00333%	29,996
African / African-American	0.00267%	37,508

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.Arg86Thr
Coding: c.257G>C
MANE Select: NM_004063
dbSNP: rs762951650
Type: single nucleotide variant
Location: chr8:94177615 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 3 PDB
Residue 86: a turn; the cadherin 1 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-arg86thr (accessed [today's date]).

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