Is CDH8 p.Gln771Arg (c.2312A>G) pathogenic?

CDH8 p.Gln771Arg (c.2312A>G) is classified Uncertain significance in CDH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1557); Absent from gnomAD v4.1.

How common is CDH8 p.Gln771Arg (c.2312A>G) in the general population?

CDH8 p.Gln771Arg (c.2312A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH8 p.Gln771Arg (c.2312A>G)?

AlphaMissense predicts likely benign (score 0.1557) — an in-silico prediction, not a clinical call.

CDH8 p.Gln771Arg

c.2312A>G · VCV4223993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1557 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1557	likely benign
REVEL	0.81	moderately pathogenic-leaning
SaProt	LLR -11.69	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 8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 136 kb · p 0.061 · regional, not allelic
Overall
CADD	26.2	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: CDH8
Protein: p.Gln771Arg
Coding: c.2312A>G
MANE Select: NM_001796
Type: single nucleotide variant
Location: chr16:61653696 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.26

Full CDH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH8 p.Arg666Cys Likely benign ★★ same type
CDH8 p.Ile429= Benign ★★ same type
CDH8 p.Tyr667= Benign/Likely benign ★★ same type
CDH8 p.Ala30Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala332Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala443Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala502Gly Uncertain significance ★ ⚠ same type
CDH8 p.Ala629Val 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/cdh8-p-gln771arg (accessed [today's date]).

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