Is CUEDC2 p.Pro20Ser (c.58C>T) pathogenic?

CUEDC2 p.Pro20Ser (c.58C>T) is classified Uncertain significance in CUEDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely benign (0.2234); Absent from gnomAD v4.1.

How common is CUEDC2 p.Pro20Ser (c.58C>T) in the general population?

CUEDC2 p.Pro20Ser (c.58C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUEDC2 p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.2234) — an in-silico prediction, not a clinical call.

CUEDC2 p.Pro20Ser

c.58C>T · VCV4657661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2234 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2234	likely benign
REVEL	0.653	pathogenic-leaning
SaProt	LLR -10.42	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 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,759 bp · p 2.4e-07 · regional, not allelic
Overall
CADD	25.4	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: CUEDC2
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_024040
Type: single nucleotide variant
Location: chr10:102425131 (GRCh38)
Gene constraint: LOEUF 0.457 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82

Full CUEDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CUEDC2 p.Ala226Ser Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala56Val Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala69Thr Uncertain significance ★ ⚠ same type
CUEDC2 p.Ala9Val Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg116Gln Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg116Trp Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg172Trp Uncertain significance ★ ⚠ same type
CUEDC2 p.Arg202Lys 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/cuedc2-p-pro20ser (accessed [today's date]).

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