Is CEP104 p.Leu309Arg (c.926T>G) pathogenic?

CEP104 p.Leu309Arg (c.926T>G) is classified Uncertain significance in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). AlphaMissense: likely benign (0.0967); Absent from gnomAD v4.1.

How common is CEP104 p.Leu309Arg (c.926T>G) in the general population?

CEP104 p.Leu309Arg (c.926T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP104 p.Leu309Arg (c.926T>G)?

AlphaMissense predicts likely benign (score 0.0967) — an in-silico prediction, not a clinical call.

CEP104 p.Leu309Arg

c.926T>G · rs1644337654 · VCV1705008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0967 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0967	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -6.45	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 6.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 37 kb · p 0.0023 · regional, not allelic
Overall
CADD	20.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP104
Protein: p.Leu309Arg
Coding: c.926T>G
MANE Select: NM_014704
dbSNP: rs1644337654
Type: single nucleotide variant
Location: chr1:3837485 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 309: a UniProt-annotated variant site (in mrt77)

Full CEP104 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP104 p.Leu309= Likely benign ★★ same residue
CEP104 c.2364+1G>A Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Arg55Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Arg631Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Glu627Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Lys270Ter Pathogenic/Likely pathogenic ★★ same type
CEP104 p.Tyr253Ter Pathogenic/Likely pathogenic ★★ 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/cep104-p-leu309arg (accessed [today's date]).

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