Is CDC45 p.Arg157His (c.470G>A) pathogenic?

CDC45 p.Arg157His (c.470G>A) is classified Uncertain significance in CDC45 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-04). AlphaMissense: likely benign (0.1002); Very rare (popmax 0.00447%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDC45 p.Arg157His (c.470G>A)?

CDC45 p.Arg157His (c.470G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDC45 p.Arg157His (c.470G>A) in the general population?

CDC45 p.Arg157His (c.470G>A) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about CDC45 p.Arg157His (c.470G>A)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

CDC45 p.Arg157His

c.470G>A · rs957839823 · VCV1895658

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -10.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	33.0	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 0.00447% East Asian · 2/44,746 alleles

Filtering AF 0.000741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000481% 7/1,455,716 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,373
African / African-American	0.00268%	37,261
South Asian	0.00112%	89,686
European (non-Finnish)	0.00017%	589,365

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.Arg157His
Coding: c.470G>A
MANE Select: NM_003504
dbSNP: rs957839823
Type: single nucleotide variant
Location: chr22:19483989 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 157: the 'disordered' region; a UniProt-annotated variant site (in mgors7; decreased protein level)

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.Arg157Cys Conflicting classifications of pathogenicity ★ ⚠ 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.Arg175Gln Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg251His Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg277Cys Uncertain significance ★★ ⚠ same condition
CDC45 p.Arg484Trp 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-arg157his (accessed [today's date]).

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