Is CEP57 p.Leu243Pro (c.728T>C) pathogenic?

CEP57 p.Leu243Pro (c.728T>C) is classified Uncertain significance in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.2805); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Leu243Pro (c.728T>C)?

CEP57 p.Leu243Pro (c.728T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CEP57 p.Leu243Pro (c.728T>C) in the general population?

CEP57 p.Leu243Pro (c.728T>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CEP57 p.Leu243Pro (c.728T>C)?

AlphaMissense predicts likely benign (score 0.2805) — an in-silico prediction, not a clinical call.

CEP57 p.Leu243Pro

c.728T>C · VCV4226384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2805	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -13.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	22.8	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 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000479% 7/1,460,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
European (non-Finnish)	8.48e-05%	1,179,398

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.Leu243Pro
Coding: c.728T>C
MANE Select: NM_014679
Type: single nucleotide variant
Location: chr11:95821899 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP57 p.Leu243Val Uncertain significance ★★ ⚠ same residue
CEP57 p.Leu243= Likely benign ★★ same residue
CEP57 p.Ala19Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala412Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala4Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala4Val Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala68Val 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-leu243pro (accessed [today's date]).

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