Is CEP120 p.Lys89Arg (c.266A>G) pathogenic?

CEP120 p.Lys89Arg (c.266A>G) is classified Uncertain significance in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). AlphaMissense: likely benign (0.0695); Very rare (popmax 0.00833%, amr).

How common is CEP120 p.Lys89Arg (c.266A>G) in the general population?

CEP120 p.Lys89Arg (c.266A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CEP120 p.Lys89Arg (c.266A>G)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

CEP120 p.Lys89Arg

c.266A>G · VCV3375609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	19.82	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00833% Admixed American · 5/60,024 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000821% 12/1,461,814 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,005
European (non-Finnish)	0.000593%	168,570

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.Lys89Arg
Coding: c.266A>G
MANE Select: NM_001375405
Type: single nucleotide variant
Location: chr5:123416065 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB
Residue 89: the c2 1 domain; a β-strand

Full CEP120 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP120 c.1255+1G>A Likely pathogenic ★★ same type
CEP120 c.2580+2T>A Likely pathogenic ★★ same type
CEP120 p.Ala199Pro Pathogenic/Likely pathogenic ★★ same type
CEP120 p.Arg722Ter Pathogenic/Likely pathogenic ★★ same type
CEP120 p.Gln775Ter Pathogenic/Likely pathogenic ★★ same type
CEP120 p.Gln808Ter Likely pathogenic ★★ same type
CEP120 p.Lys539Ter Pathogenic/Likely pathogenic ★★ same type
CEP120 c.1038+6T>C Uncertain significance ★★ same type

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-lys89arg (accessed [today's date]).

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