Is CEP57 p.Ser7fs (c.20_21del) pathogenic?

CEP57 p.Ser7fs (c.2021del) is classified Pathogenic in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). Very rare (popmax 8.47e-05%, nfe); Associated with mosaic variegated aneuploidy syndrome 2.

What condition is associated with CEP57 p.Ser7fs (c.20_21del)?

CEP57 p.Ser7fs (c.20_21del) is associated with mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ser7fs (c.20_21del) in the general population?

CEP57 p.Ser7fs (c.20_21del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CEP57 p.Ser7fs

c.20_21del · rs2496049330 · VCV2169972

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)

Conditions

mosaic variegated aneuploidy syndrome 2

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 1 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	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) · 1/1,180,006 alleles

Overall 6.84e-05% 1/1,461,756 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: CEP57
Protein: p.Ser7fs
Coding: c.20_21del
MANE Select: NM_014679
dbSNP: rs2496049330
Type: Microsatellite
Location: chr11:95790715 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 7: the 'disordered' region

Full CEP57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mosaic variegated aneuploidy syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP57 p.Ser7Phe Uncertain significance ★★ ⚠ same residue
CEP57 p.Ser7= Likely benign ★★ same residue
CEP57 p.Tyr104_Lys105delinsTer Pathogenic ★ same condition
CEP57 c.45+11_45+12insGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCATGAGGTCAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAAGCAG Uncertain significance ★ same condition
CEP57 c.504+5_504+8del Uncertain significance ★ same condition
CEP57 c.808-11_808-7del Uncertain significance ★ same condition
CEP57 p.Arg474fs Uncertain significance ★ same condition
CEP57 p.Lys435del 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/cep57-p-ser7fs (accessed [today's date]).

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