Is CDH9 p.Arg773Leu (c.2318G>T) pathogenic?

CDH9 p.Arg773Leu (c.2318G>T) is classified Uncertain significance in CDH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.2554); Absent from gnomAD v4.1.

How common is CDH9 p.Arg773Leu (c.2318G>T) in the general population?

CDH9 p.Arg773Leu (c.2318G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH9 p.Arg773Leu (c.2318G>T)?

AlphaMissense predicts likely benign (score 0.2554) — an in-silico prediction, not a clinical call.

CDH9 p.Arg773Leu

c.2318G>T · rs553402369 · VCV3141348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2554 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2554	likely benign
REVEL	0.713	pathogenic-leaning
SaProt	LLR -13.77	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 107 kb · p 0.00043 · regional, not allelic
Overall
CADD	28.1	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

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: CDH9
Protein: p.Arg773Leu
Coding: c.2318G>T
MANE Select: NM_016279
dbSNP: rs553402369
Type: single nucleotide variant
Location: chr5:26881188 (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.Arg773His Uncertain significance ★ ⚠ same residue
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

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-arg773leu (accessed [today's date]).

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