Is CDH9 p.Glu643Asp (c.1929A>C) pathogenic?

CDH9 p.Glu643Asp (c.1929A>C) is classified Uncertain significance in CDH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: ambiguous (0.3667); Very rare (popmax 0.00263%, nfe).

How common is CDH9 p.Glu643Asp (c.1929A>C) in the general population?

CDH9 p.Glu643Asp (c.1929A>C) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about CDH9 p.Glu643Asp (c.1929A>C)?

AlphaMissense predicts ambiguous (score 0.3667) — an in-silico prediction, not a clinical call.

CDH9 p.Glu643Asp

c.1929A>C · VCV3999085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3667 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3667	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -9.44	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.9
Regional constraint	o/e 0.89	unconstrained · MANE · 107 kb · p 0.00043 · regional, not allelic
Overall
CADD	12.26	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 0.00263% European (non-Finnish) · 31/1,179,422 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00192% 31/1,612,302 alleles · very 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: CDH9
Protein: p.Glu643Asp
Coding: c.1929A>C
MANE Select: NM_016279
Type: single nucleotide variant
Location: chr5:26881577 (GRCh38)
Gene constraint: LOEUF 0.578 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 77.60

Full CDH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH9 p.Arg53Cys Uncertain significance ★★ ⚠ same type
CDH9 p.Glu603Gly Benign ★★ ⚠ same type
CDH9 p.Pro486= Benign ★★ same type
CDH9 p.Ala186Thr Uncertain significance ★ ⚠ same type
CDH9 p.Ala412Ser Uncertain significance ★ ⚠ same type
CDH9 p.Ala445Gly Uncertain significance ★ ⚠ same type
CDH9 p.Ala500Glu Uncertain significance ★ ⚠ same type
CDH9 p.Arg137Gln 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/cdh9-p-glu643asp (accessed [today's date]).

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