Is CDH20 p.Gln648Pro (c.1943A>C) pathogenic?

CDH20 p.Gln648Pro (c.1943A>C) is classified Uncertain significance in CDH20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: likely benign (0.1087); Very rare (popmax 0.00915%, nfe).

How common is CDH20 p.Gln648Pro (c.1943A>C) in the general population?

CDH20 p.Gln648Pro (c.1943A>C) is very rare (popmax 0.00915%, nfe) (gnomAD).

What do computational predictors say about CDH20 p.Gln648Pro (c.1943A>C)?

AlphaMissense predicts likely benign (score 0.1087) — an in-silico prediction, not a clinical call.

CDH20 p.Gln648Pro

c.1943A>C · VCV3265237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00915%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1087	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.69, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 4,569 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	23.4	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

Grpmax group 0.00915% European (non-Finnish) · 108/1,179,866 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00731% 118/1,613,698 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00915%	10,925
Remaining individualsnot grpmax-eligible	0.008%	12,495
African / African-American	0.00534%	18,730
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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: CDH20
Protein: p.Gln648Pro
Coding: c.1943A>C
MANE Select: NM_031891
Type: single nucleotide variant
Location: chr18:61554232 (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-gln648pro (accessed [today's date]).

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