Is CDH20 p.Cys716Ser (c.2146T>A) pathogenic?

CDH20 p.Cys716Ser (c.2146T>A) is classified Uncertain significance in CDH20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.095); Absent from gnomAD v4.1.

How common is CDH20 p.Cys716Ser (c.2146T>A) in the general population?

CDH20 p.Cys716Ser (c.2146T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH20 p.Cys716Ser (c.2146T>A)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

CDH20 p.Cys716Ser

c.2146T>A · VCV4835717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -3.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.16	GERP 1.9, phastCons 0.022
Regional constraint	o/e 1.28	unconstrained · MANE · 4,569 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	18.78	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CDH20
Protein: p.Cys716Ser
Coding: c.2146T>A
MANE Select: NM_031891
Type: single nucleotide variant
Location: chr18:61554435 (GRCh38)
Gene constraint: LOEUF 0.532 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 77.33

Full CDH20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH20 p.Arg687Trp Uncertain significance ★★ ⚠ same type
CDH20 p.Pro39= Benign ★★ same type
CDH20 p.Ala226Val Uncertain significance ★ ⚠ same type
CDH20 p.Ala403Val Uncertain significance ★ ⚠ same type
CDH20 p.Ala506Thr Uncertain significance ★ ⚠ same type
CDH20 p.Ala610Val Uncertain significance ★ ⚠ same type
CDH20 p.Ala627Thr Uncertain significance ★ ⚠ same type
CDH20 p.Ala691Thr 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/cdh20-p-cys716ser (accessed [today's date]).

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