Is CEP57 p.Leu367= (c.1099T>C) pathogenic?

CEP57 p.Leu367= (c.1099T>C) is classified Likely benign in CEP57 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-08). Ultra-rare (popmax 0.0286%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Leu367= (c.1099T>C)?

CEP57 p.Leu367= (c.1099T>C) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Leu367= (c.1099T>C) in the general population?

CEP57 p.Leu367= (c.1099T>C) is ultra-rare (popmax 0.0286%, sas) (gnomAD).

CEP57 p.Leu367=

c.1099T>C · rs759922227 · VCV1546989

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0286%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.013	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.43	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.1	GERP -4.9, phastCons 0.86
Overall
CADD	7.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0286% South Asian · 26/91,068 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0018% 29/1,613,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0286%	3,503
Remaining individualsnot grpmax-eligible	0.0016%	62,486
Finnishnot grpmax-eligible	0.00156%	64,006
European (non-Finnish)	8.47e-05%	1,179,997

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.Leu367=
Coding: c.1099T>C
MANE Select: NM_014679
dbSNP: rs759922227
Type: single nucleotide variant
Location: chr11:95827999 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 367: an α-helix; 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.Leu367Ile Uncertain significance ★★ ⚠ same residue
CEP57 p.Leu367Ser 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-leu367 (accessed [today's date]).

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