Is CDC40 p.Gln346Glu (c.1036C>G) pathogenic?

CDC40 p.Gln346Glu (c.1036C>G) is classified Uncertain significance in CDC40 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.122); Absent from gnomAD v4.1.

How common is CDC40 p.Gln346Glu (c.1036C>G) in the general population?

CDC40 p.Gln346Glu (c.1036C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC40 p.Gln346Glu (c.1036C>G)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

CDC40 p.Gln346Glu

c.1036C>G · rs2534455814 · VCV2526522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 39 kb · p 5.5e-07 · regional, not allelic
Overall
CADD	21.8	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: CDC40
Protein: p.Gln346Glu
Coding: c.1036C>G
MANE Select: NM_015891
dbSNP: rs2534455814
Type: single nucleotide variant
Location: chr6:110217749 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.76 · 30 PDB
Residue 346: a β-strand

Full CDC40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC40 p.Ala33Gly Uncertain significance ★ ⚠ same type
CDC40 p.Ala466Thr Uncertain significance ★ ⚠ same type
CDC40 p.Arg129Lys Uncertain significance ★ ⚠ same type
CDC40 p.Arg322Trp Uncertain significance ★ ⚠ same type
CDC40 p.Arg323Cys Uncertain significance ★ ⚠ same type
CDC40 p.Asn382His Uncertain significance ★ ⚠ same type
CDC40 p.Asn430Lys Uncertain significance ★ ⚠ same type
CDC40 p.Asn497Thr 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/cdc40-p-gln346glu (accessed [today's date]).

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