Is CDC45 p.Lys482fs (c.1445_1448del) pathogenic?

CDC45 p.Lys482fs (c.14451448del) is classified Pathogenic in CDC45 (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 8.48e-05%, nfe); Associated with Meier-Gorlin syndrome 7.

What condition is associated with CDC45 p.Lys482fs (c.1445_1448del)?

CDC45 p.Lys482fs (c.1445_1448del) is associated with Meier-Gorlin syndrome 7 (ClinVar).

How common is CDC45 p.Lys482fs (c.1445_1448del) in the general population?

CDC45 p.Lys482fs (c.1445_1448del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CDC45 p.Lys482fs

c.1445_1448del · rs1933800287 · VCV1162262

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Meier-Gorlin syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.4, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,482 alleles

Overall 0.000658% 1/152,084 alleles · very rare

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.Lys482fs
Coding: c.1445_1448del
MANE Select: NM_003504
dbSNP: rs1933800287
Type: Deletion
Location: chr22:19516529 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 482: 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

Meier-Gorlin syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDC45 c.(342+1_343-1 Pathogenic same condition
CDC45 p.Asn111fs Pathogenic ★★ same condition
CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
CDC45 p.Ile509Val Uncertain significance ★★ ⚠ same condition
CDC45 p.Pro496Leu Uncertain significance ★★ ⚠ same condition
CDC45 p.Ala298Val Likely pathogenic ★ ⚠ same condition
CDC45 p.Asn76His Likely pathogenic ★ same condition
CDC45 p.Asp226Gly Likely pathogenic ★ ⚠ 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-lys482fs (accessed [today's date]).

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