Is CDC45 p.Arg485Cys (c.1453C>T) pathogenic?

CDC45 p.Arg485Cys (c.1453C>T) is classified Uncertain significance in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: ambiguous (0.368); Very rare (popmax 0.00401%, afr).

How common is CDC45 p.Arg485Cys (c.1453C>T) in the general population?

CDC45 p.Arg485Cys (c.1453C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about CDC45 p.Arg485Cys (c.1453C>T)?

AlphaMissense predicts ambiguous (score 0.368) — an in-silico prediction, not a clinical call.

CDC45 p.Arg485Cys

c.1453C>T · rs757736626 · VCV2071862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.368 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
AlphaMissense	0.368	ambiguous
REVEL	0.465	indeterminate
SaProt	LLR -10.77	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	32.0	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 0.00401% African / African-American · 3/74,862 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00229% 37/1,613,630 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,954
European (non-Finnish)	0.00288%	34,699

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.Arg485Cys
Coding: c.1453C>T
MANE Select: NM_003504
dbSNP: rs757736626
Type: single nucleotide variant
Location: chr22:19516539 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 485: a UniProt-annotated variant site (in mgors7; likely pathogenic)

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

Similar variants

CDC45 p.Arg485His Uncertain significance ★ ⚠ same residue
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

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-arg485cys (accessed [today's date]).

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