Is CDC45 p.Glu67Gln (c.199G>C) pathogenic?

CDC45 p.Glu67Gln (c.199G>C) is classified Conflicting classifications of pathogenicity in CDC45 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-30). AlphaMissense: likely benign (0.1736); Rare (popmax 0.103%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDC45 p.Glu67Gln (c.199G>C)?

CDC45 p.Glu67Gln (c.199G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CDC45 p.Glu67Gln (c.199G>C) in the general population?

CDC45 p.Glu67Gln (c.199G>C) is rare (popmax 0.103%, eas) (gnomAD).

What do computational predictors say about CDC45 p.Glu67Gln (c.199G>C)?

AlphaMissense predicts likely benign (score 0.1736) — an in-silico prediction, not a clinical call.

CDC45 p.Glu67Gln

c.199G>C · rs545468684 · VCV1521210

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1736 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1736	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.36, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.0069 · regional, not allelic
Overall
CADD	25.0	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 0.103% East Asian · 46/44,858 alleles

Filtering AF 0.079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0707%

Overall 0.00323% 52/1,608,296 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.103%	975
Admixed American	0.00501%	19,979
Remaining individualsnot grpmax-eligible	0.00481%	20,769

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.Glu67Gln
Coding: c.199G>C
MANE Select: NM_003504
dbSNP: rs545468684
Type: single nucleotide variant
Location: chr22:19481040 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 67: a turn

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 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
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-glu67gln (accessed [today's date]).

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