Is CDC45 p.Ser264fs (c.790_791del) pathogenic?

CDC45 p.Ser264fs (c.790791del) is classified Pathogenic in CDC45 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Very rare (popmax 0.0011%, sas).

How common is CDC45 p.Ser264fs (c.790_791del) in the general population?

CDC45 p.Ser264fs (c.790_791del) is very rare (popmax 0.0011%, sas) (gnomAD).

CDC45 p.Ser264fs

c.790_791del · rs763515165 · VCV1373744

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 10 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,062 alleles

Overall 0.000137% 2/1,461,728 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,062
European (non-Finnish)	8.48e-05%	1,179,860

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.Ser264fs
Coding: c.790_791del
MANE Select: NM_003504
dbSNP: rs763515165
Type: Microsatellite
Location: chr22:19505444 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.59 · 7 PDB
Residue 264: a UniProt-annotated variant site (in mgors7; uncertain significance)

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

Similar variants

CDC45 p.Ser264= Likely benign ★★ same residue
CDC45 p.Ser264Tyr Uncertain significance ★ same residue
CDC45 p.Asn111fs Pathogenic ★★ same type
CDC45 c.1055+5AC[2] Likely benign ★★ same type
CDC45 p.Val305fs 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-ser264fs (accessed [today's date]).

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