Is CEP120 p.Pro488Ser (c.1462C>T) pathogenic?

CEP120 p.Pro488Ser (c.1462C>T) is classified Uncertain significance in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely pathogenic (0.6785); Very rare (popmax 8.94e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP120 p.Pro488Ser (c.1462C>T)?

CEP120 p.Pro488Ser (c.1462C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP120 p.Pro488Ser (c.1462C>T) in the general population?

CEP120 p.Pro488Ser (c.1462C>T) is very rare (popmax 8.94e-05%, nfe) (gnomAD).

What do computational predictors say about CEP120 p.Pro488Ser (c.1462C>T)?

AlphaMissense predicts likely pathogenic (score 0.6785) — an in-silico prediction, not a clinical call.

CEP120 p.Pro488Ser

c.1462C>T · VCV4612445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6785 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.94e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6785	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -10.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.94e-05% European (non-Finnish) · 1/1,118,622 alleles

Overall 7.31e-05% 1/1,368,218 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: CEP120
Protein: p.Pro488Ser
Coding: c.1462C>T
MANE Select: NM_001375405
Type: single nucleotide variant
Location: chr5:123386636 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 488: the c2 2 domain

Full CEP120 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

CEP120 p.Arg611Cys Uncertain significance ★★ ⚠ same condition
CEP120 p.Arg611Leu Uncertain significance ★★ ⚠ same condition
CEP120 p.Arg722Gln Uncertain significance ★★ ⚠ same condition
CEP120 p.Arg722Pro Uncertain significance ★★ ⚠ same condition
CEP120 p.Arg746Gln Uncertain significance ★★ ⚠ same condition
CEP120 p.Arg904Ile Uncertain significance ★★ ⚠ same condition
CEP120 p.Asn242His Uncertain significance ★★ ⚠ same condition
CEP120 p.Asn435Ser 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/cep120-p-pro488ser (accessed [today's date]).

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