Is CDC45 p.His472= (c.1416C>T) pathogenic?

CDC45 p.His472= (c.1416C>T) is classified Conflicting classifications of pathogenicity in CDC45 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-18). Rare (popmax 0.145%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDC45 p.His472= (c.1416C>T)?

CDC45 p.His472= (c.1416C>T) is associated with Inborn genetic diseases, Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.His472= (c.1416C>T) in the general population?

CDC45 p.His472= (c.1416C>T) is rare (popmax 0.145%, eas) (gnomAD).

CDC45 p.His472=

c.1416C>T · rs190155337 · VCV872335

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.145%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -1.8, phastCons 0.001
Overall
CADD	4.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% East Asian · 65/44,852 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00552% 89/1,612,490 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.145%	690
South Asian	0.0143%	6,991
Remaining individualsnot grpmax-eligible	0.00961%	10,406
Admixed American	0.00167%	59,954
African / African-American	0.00133%	74,998
European (non-Finnish)	0.000254%	392,984

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.His472=
Coding: c.1416C>T
MANE Select: NM_003504
dbSNP: rs190155337
Type: single nucleotide variant
Location: chr22:19515024 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 472: a UniProt-annotated variant site (in mgors7; likely pathogenic); 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

Also linked: Meier-Gorlin syndrome 7

Similar variants

CDC45 p.His472Asn Uncertain significance ★ ⚠ same residue
CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
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

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-his472 (accessed [today's date]).

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