Is CDC45 p.Val305fs (c.914_915del) pathogenic?

CDC45 p.Val305fs (c.914915del) is classified Pathogenic in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-03). Very rare (popmax 8.47e-05%, nfe).

How common is CDC45 p.Val305fs (c.914_915del) in the general population?

CDC45 p.Val305fs (c.914_915del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CDC45 p.Val305fs

c.914_915del · rs2146413876 · VCV1069021

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 11 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,190 alleles · very rare exomes 1/1,461,852 · genomes 0/152,338 · joint denominator

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.Val305fs
Coding: c.914_915del
MANE Select: NM_003504
dbSNP: rs2146413876
Type: Microsatellite
Location: chr22:19507473 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 305: an α-helix

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

Similar variants

CDC45 p.Asn111fs Pathogenic ★★ same type
CDC45 c.1055+5AC[2] Likely benign ★★ same type
CDC45 p.Ser264fs Pathogenic ★ same type
CDC45 c.112-12CT[3] Likely benign ★ same type
CDC45 c.704+7AC[2] Likely benign ★ 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-val305fs (accessed [today's date]).

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