Is CEP120 p.Pro43Arg (c.128C>G) pathogenic?

CEP120 p.Pro43Arg (c.128C>G) is classified Uncertain significance in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: ambiguous (0.4463); Very rare (popmax 0.00153%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP120 p.Pro43Arg (c.128C>G)?

CEP120 p.Pro43Arg (c.128C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP120 p.Pro43Arg (c.128C>G) in the general population?

CEP120 p.Pro43Arg (c.128C>G) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about CEP120 p.Pro43Arg (c.128C>G)?

AlphaMissense predicts ambiguous (score 0.4463) — an in-silico prediction, not a clinical call.

CEP120 p.Pro43Arg

c.128C>G · VCV3831638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4463 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4463	ambiguous
REVEL	0.628	indeterminate
SaProt	LLR -14.06	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	28.4	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 0.00153% European (non-Finnish) · 18/1,179,188 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,612,872 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.Pro43Arg
Coding: c.128C>G
MANE Select: NM_001375405
Type: single nucleotide variant
Location: chr5:123418437 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 43: the c2 1 domain; an α-helix

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-pro43arg (accessed [today's date]).

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