Is CDC45 p.Arg484Trp (c.1450C>T) pathogenic?

CDC45 p.Arg484Trp (c.1450C>T) is classified Uncertain significance in CDC45 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-04). AlphaMissense: likely benign (0.2526); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDC45 p.Arg484Trp (c.1450C>T)?

CDC45 p.Arg484Trp (c.1450C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDC45 p.Arg484Trp (c.1450C>T) in the general population?

CDC45 p.Arg484Trp (c.1450C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CDC45 p.Arg484Trp (c.1450C>T)?

AlphaMissense predicts likely benign (score 0.2526) — an in-silico prediction, not a clinical call.

CDC45 p.Arg484Trp

c.1450C>T · rs371699135 · VCV1985375

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2526 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2526	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -10.20	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 5	GERP 0.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	29.8	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

Grpmax group 0.00801% African / African-American · 6/74,862 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00211% 34/1,613,608 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,477
Remaining individualsnot grpmax-eligible	0.0032%	31,233
East Asian	0.00223%	44,878
European (non-Finnish)	0.00203%	49,156
Finnishnot grpmax-eligible	0.00156%	63,988

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: CDC45
Protein: p.Arg484Trp
Coding: c.1450C>T
MANE Select: NM_003504
dbSNP: rs371699135
Type: single nucleotide variant
Location: chr22:19516536 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 484: a UniProt-annotated variant site (in mgors7; likely pathogenic)

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.Arg484Gln 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-arg484trp (accessed [today's date]).

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