Is CEP57 p.Ser41Leu (c.122C>T) pathogenic?

CEP57 p.Ser41Leu (c.122C>T) is classified Uncertain significance in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-30). AlphaMissense: likely benign (0.0771); Ultra-rare (popmax 0.0164%, mid); Associated with mosaic variegated aneuploidy syndrome 2.

What condition is associated with CEP57 p.Ser41Leu (c.122C>T)?

CEP57 p.Ser41Leu (c.122C>T) is associated with mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ser41Leu (c.122C>T) in the general population?

CEP57 p.Ser41Leu (c.122C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CEP57 p.Ser41Leu (c.122C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

CEP57 p.Ser41Leu

c.122C>T · rs993520814 · VCV641896

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mosaic variegated aneuploidy syndrome 2

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.9	GERP 0.73, phastCons 0.9
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	18.73	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00335% 54/1,613,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.005%	20,002
European (non-Finnish)	0.0039%	25,650
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
East Asian	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asian	0.0011%	91,084

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.Ser41Leu
Coding: c.122C>T
MANE Select: NM_014679
dbSNP: rs993520814
Type: single nucleotide variant
Location: chr11:95799308 (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.Ser41= 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-ser41leu (accessed [today's date]).

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