Is CEP57 p.Arg258= (c.772A>C) pathogenic?

CEP57 p.Arg258= (c.772A>C) is classified Likely benign in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-21). Absent from gnomAD v4.1; Associated with mosaic variegated aneuploidy syndrome 2.

What condition is associated with CEP57 p.Arg258= (c.772A>C)?

CEP57 p.Arg258= (c.772A>C) is associated with mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Arg258= (c.772A>C) in the general population?

CEP57 p.Arg258= (c.772A>C) is absent from gnomAD v4.1 (gnomAD).

CEP57 p.Arg258=

c.772A>C · rs2496284340 · VCV2005522

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

mosaic variegated aneuploidy syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.127	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.1	GERP 2.4, phastCons 1
Overall
CADD	12.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP57
Protein: p.Arg258=
Coding: c.772A>C
MANE Select: NM_014679
dbSNP: rs2496284340
Type: single nucleotide variant
Location: chr11:95821943 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB

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.Arg258Gly 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
CEP57 p.Ala412Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala423Thr 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-arg258 (accessed [today's date]).

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