Is CEP57 p.Ser34Pro (c.100T>C) pathogenic?

CEP57 p.Ser34Pro (c.100T>C) is classified Uncertain significance in CEP57 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.1021); Rare (popmax 0.102%, amr); Associated with mosaic variegated aneuploidy syndrome 2.

What condition is associated with CEP57 p.Ser34Pro (c.100T>C)?

CEP57 p.Ser34Pro (c.100T>C) is associated with mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ser34Pro (c.100T>C) in the general population?

CEP57 p.Ser34Pro (c.100T>C) is rare (popmax 0.102%, amr) (gnomAD).

What do computational predictors say about CEP57 p.Ser34Pro (c.100T>C)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

CEP57 p.Ser34Pro

c.100T>C · rs760029883 · VCV950469

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 2

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
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	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% Admixed American · 61/60,012 alleles

Filtering AF 0.0811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0738%

Overall 0.00384% 62/1,614,050 alleles · rare exomes 56/1,461,806 · genomes 6/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.102%	984
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ser34Pro
Coding: c.100T>C
MANE Select: NM_014679
dbSNP: rs760029883
Type: single nucleotide variant
Location: chr11:95799286 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 34: 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.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-ser34pro (accessed [today's date]).

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