Is CDC45 p.Leu340Phe (c.1020G>C) pathogenic?

CDC45 p.Leu340Phe (c.1020G>C) is classified Uncertain significance in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely benign (0.2655); Absent from gnomAD v4.1.

How common is CDC45 p.Leu340Phe (c.1020G>C) in the general population?

CDC45 p.Leu340Phe (c.1020G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC45 p.Leu340Phe (c.1020G>C)?

AlphaMissense predicts likely benign (score 0.2655) — an in-silico prediction, not a clinical call.

CDC45 p.Leu340Phe

c.1020G>C · rs1198413149 · VCV1022452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2655 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2655	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -10.08	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 2.2	GERP -1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	18.94	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: CDC45
Protein: p.Leu340Phe
Coding: c.1020G>C
MANE Select: NM_003504
dbSNP: rs1198413149
Type: single nucleotide variant
Location: chr22:19507829 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 340: an α-helix

Full CDC45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
CDC45 c.653+4C>T Uncertain significance ★★ same type
CDC45 p.Ala373Val Uncertain significance ★★ ⚠ same type
CDC45 p.Ala38Asp Uncertain significance ★★ ⚠ same type
CDC45 p.Arg157His Uncertain significance ★★ ⚠ same type
CDC45 p.Arg175Gln Uncertain significance ★★ ⚠ same type
CDC45 p.Arg251His Uncertain significance ★★ ⚠ same type
CDC45 p.Arg269Trp 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/cdc45-p-leu340phe (accessed [today's date]).

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