Is CEP120 p.Arg646Gly (c.1936C>G) pathogenic?

CEP120 p.Arg646Gly (c.1936C>G) is classified Uncertain significance in CEP120 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). AlphaMissense: likely pathogenic (0.7989); Very rare (popmax 0.00178%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP120 p.Arg646Gly (c.1936C>G)?

CEP120 p.Arg646Gly (c.1936C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP120 p.Arg646Gly (c.1936C>G) in the general population?

CEP120 p.Arg646Gly (c.1936C>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about CEP120 p.Arg646Gly (c.1936C>G)?

AlphaMissense predicts likely pathogenic (score 0.7989) — an in-silico prediction, not a clinical call.

CEP120 p.Arg646Gly

c.1936C>G · VCV3265975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7989	likely pathogenic
REVEL	0.407	indeterminate
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 76 kb · p 0.029 · regional, not allelic
Overall
CADD	24.8	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 0.00178% European (non-Finnish) · 21/1,179,626 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,613,216 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.Arg646Gly
Coding: c.1936C>G
MANE Select: NM_001375405
Type: single nucleotide variant
Location: chr5:123382814 (GRCh38)
Gene constraint: LOEUF 0.93 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.22 · 4 PDB

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.Arg646His Uncertain significance ★★ ⚠ same residue
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

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-arg646gly (accessed [today's date]).

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