Is CDH6 p.Ser200Arg (c.598A>C) pathogenic?

CDH6 p.Ser200Arg (c.598A>C) is classified Uncertain significance in CDH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely pathogenic (0.9337); Absent from gnomAD v4.1.

How common is CDH6 p.Ser200Arg (c.598A>C) in the general population?

CDH6 p.Ser200Arg (c.598A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH6 p.Ser200Arg (c.598A>C)?

AlphaMissense predicts likely pathogenic (score 0.9337) — an in-silico prediction, not a clinical call.

CDH6 p.Ser200Arg

c.598A>C · VCV3830212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9337 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9337	likely pathogenic
REVEL	0.703	pathogenic-leaning
SaProt	LLR -10.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 50 kb · p 7.7e-20 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CDH6
Protein: p.Ser200Arg
Coding: c.598A>C
MANE Select: NM_004932
Type: single nucleotide variant
Location: chr5:31297363 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 78.67 · 1 PDB
Residue 200: the cadherin 2 domain

Full CDH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH6 p.Ala130Val Uncertain significance ★ ⚠ same type
CDH6 p.Ala489Ser Uncertain significance ★ ⚠ same type
CDH6 p.Ala634Gly Uncertain significance ★ ⚠ same type
CDH6 p.Ala671Ser Uncertain significance ★ ⚠ same type
CDH6 p.Ala706Val Uncertain significance ★ ⚠ same type
CDH6 p.Ala729Val Uncertain significance ★ ⚠ same type
CDH6 p.Ala739Val Uncertain significance ★ ⚠ same type
CDH6 p.Arg115Lys 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/cdh6-p-ser200arg (accessed [today's date]).

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