Is CEP57 p.Ser343Arg (c.1029T>A) pathogenic?

CEP57 p.Ser343Arg (c.1029T>A) is classified Uncertain significance in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-14). AlphaMissense: likely benign (0.1756); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Ser343Arg (c.1029T>A)?

CEP57 p.Ser343Arg (c.1029T>A) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ser343Arg (c.1029T>A) in the general population?

CEP57 p.Ser343Arg (c.1029T>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about CEP57 p.Ser343Arg (c.1029T>A)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

CEP57 p.Ser343Arg

c.1029T>A · rs539891523 · VCV1357666

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.015	GERP -4.9, phastCons 0.39
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	13.3	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 0.0133% African / African-American · 10/75,032 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00124% 20/1,614,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,503
European (non-Finnish)	0.000847%	117,999

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.Ser343Arg
Coding: c.1029T>A
MANE Select: NM_014679
dbSNP: rs539891523
Type: single nucleotide variant
Location: chr11:95827929 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 343: the 'mediates interaction with microtubules' 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.Ser343Thr Uncertain significance ★★ ⚠ same residue
CEP57 p.Ser343Asn 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

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-ser343arg (accessed [today's date]).

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