Is CEP57 p.Pro54= (c.162A>G) pathogenic?

CEP57 p.Pro54= (c.162A>G) is classified Likely benign in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-05). Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Pro54= (c.162A>G)?

CEP57 p.Pro54= (c.162A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP57 p.Pro54= (c.162A>G) in the general population?

CEP57 p.Pro54= (c.162A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CEP57 p.Pro54=

c.162A>G · VCV3831957

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP -4.8, phastCons 1
Overall
CADD	9.858	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,960 alleles

Overall 6.84e-05% 1/1,461,732 alleles · very rare

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.Pro54=
Coding: c.162A>G
MANE Select: NM_014679
Type: single nucleotide variant
Location: chr11:95799348 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 54: the 'disordered' 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

Similar variants

CEP57 p.Pro54Ala Uncertain significance ★ ⚠ same residue
CEP57 p.Pro54Arg Uncertain significance ★ ⚠ 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-pro54 (accessed [today's date]).

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