Is CEP57 p.Leu50= (c.150A>C) pathogenic?

CEP57 p.Leu50= (c.150A>C) is classified Likely benign in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Leu50= (c.150A>C)?

CEP57 p.Leu50= (c.150A>C) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Leu50= (c.150A>C) in the general population?

CEP57 p.Leu50= (c.150A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CEP57 p.Leu50=

c.150A>C · rs190360114 · VCV1532034

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

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

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 -0.36	GERP -4.8, phastCons 0.002
Overall
CADD	4.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 0.000657% 1/152,214 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.Leu50=
Coding: c.150A>C
MANE Select: NM_014679
dbSNP: rs190360114
Type: single nucleotide variant
Location: chr11:95799336 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 50: the 'disordered' region

Full CEP57 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: mosaic variegated aneuploidy syndrome 2

Similar variants

CEP57 p.Leu50Ile Uncertain significance ★★ ⚠ same residue
CEP57 p.Leu50Arg Uncertain significance ★ ⚠ same residue
CEP57 p.Leu50Val Uncertain significance ★ ⚠ same residue
CEP57 p.Arg339Ter Pathogenic ★★ same condition
CEP57 c.202+6C>T Uncertain significance ★★ same condition
CEP57 p.Ala19Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Val 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-leu50 (accessed [today's date]).

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