Is CEP57 p.Ser163Pro (c.487T>C) pathogenic?

CEP57 p.Ser163Pro (c.487T>C) is classified Uncertain significance in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-27). AlphaMissense: likely pathogenic (0.8893); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Ser163Pro (c.487T>C)?

CEP57 p.Ser163Pro (c.487T>C) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ser163Pro (c.487T>C) in the general population?

CEP57 p.Ser163Pro (c.487T>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CEP57 p.Ser163Pro (c.487T>C)?

AlphaMissense predicts likely pathogenic (score 0.8893) — an in-silico prediction, not a clinical call.

CEP57 p.Ser163Pro

c.487T>C · rs2496227190 · VCV2764742

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8893	likely pathogenic · top 10% in CEP57
REVEL	0.189	benign-leaning
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,926 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000479% 7/1,460,762 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.Ser163Pro
Coding: c.487T>C
MANE Select: NM_014679
dbSNP: rs2496227190
Type: single nucleotide variant
Location: chr11:95813572 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 163: the 'centrosome localization domain (cld)' 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.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
CEP57 p.Ala4Gly 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-ser163pro (accessed [today's date]).

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