Is CEP57 p.Ala302Asp (c.905C>A) pathogenic?

CEP57 p.Ala302Asp (c.905C>A) is classified Uncertain significance in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-20). AlphaMissense: likely pathogenic (0.9113); Absent from gnomAD v4.1; Associated with mosaic variegated aneuploidy syndrome 2.

What condition is associated with CEP57 p.Ala302Asp (c.905C>A)?

CEP57 p.Ala302Asp (c.905C>A) is associated with mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ala302Asp (c.905C>A) in the general population?

CEP57 p.Ala302Asp (c.905C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP57 p.Ala302Asp (c.905C>A)?

AlphaMissense predicts likely pathogenic (score 0.9113) — an in-silico prediction, not a clinical call.

CEP57 p.Ala302Asp

c.905C>A · rs2496324527 · VCV2100608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9113 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mosaic variegated aneuploidy syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9113	likely pathogenic · top 9% in CEP57
REVEL	0.349	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala302Asp
Coding: c.905C>A
MANE Select: NM_014679
dbSNP: rs2496324527
Type: single nucleotide variant
Location: chr11:95827805 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 302: the 'mediates interaction with microtubules' 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.Ala302= Likely benign ★★ 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-ala302asp (accessed [today's date]).

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