Is CDC45 p.Ala297Val (c.890C>T) pathogenic?

CDC45 p.Ala297Val (c.890C>T) is classified Uncertain significance in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-06). AlphaMissense: likely benign (0.1274); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDC45 p.Ala297Val (c.890C>T)?

CDC45 p.Ala297Val (c.890C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDC45 p.Ala297Val (c.890C>T) in the general population?

CDC45 p.Ala297Val (c.890C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDC45 p.Ala297Val (c.890C>T)?

AlphaMissense predicts likely benign (score 0.1274) — an in-silico prediction, not a clinical call.

CDC45 p.Ala297Val

c.890C>T · rs2517653728 · VCV2294180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1274 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1274	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	24.5	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: CDC45
Protein: p.Ala297Val
Coding: c.890C>T
MANE Select: NM_003504
dbSNP: rs2517653728
Type: single nucleotide variant
Location: chr22:19507451 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 297: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC45 p.Ala297Thr Uncertain significance ★ ⚠ same residue
CDC45 c.653+4C>T Uncertain significance ★★ same condition
CDC45 p.Ala373Val Uncertain significance ★★ ⚠ same condition
CDC45 p.Ala38Asp Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg157His Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg175Gln Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg251His Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg277Cys Uncertain significance ★★ ⚠ same condition

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-ala297val (accessed [today's date]).

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