Is CEP41 p.Pro280Ala (c.838C>G) pathogenic?

CEP41 p.Pro280Ala (c.838C>G) is classified Uncertain significance in CEP41 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-19). AlphaMissense: likely benign (0.0563); Absent from gnomAD v4.1; Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Pro280Ala (c.838C>G)?

CEP41 p.Pro280Ala (c.838C>G) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Pro280Ala (c.838C>G) in the general population?

CEP41 p.Pro280Ala (c.838C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP41 p.Pro280Ala (c.838C>G)?

AlphaMissense predicts likely benign (score 0.0563) — an in-silico prediction, not a clinical call.

CEP41 p.Pro280Ala

c.838C>G · VCV4745533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0563 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.0563	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -6.99	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 3.9	GERP 0.72, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	16.16	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: CEP41
Protein: p.Pro280Ala
Coding: c.838C>G
MANE Select: NM_018718
Type: single nucleotide variant
Location: chr7:130400174 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 280: the 'disordered' region

Full CEP41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP41 c.34-2A>G Pathogenic/Likely pathogenic ★★ same condition
CEP41 c.423-2A>C Pathogenic ★★ same condition
CEP41 p.Arg286Ter Pathogenic/Likely pathogenic ★★ same condition
CEP41 p.Gln140Ter Pathogenic ★★ same condition
CEP41 c.33+6G>A Uncertain significance ★★ same condition
CEP41 c.*2116T>C Uncertain significance ★★ same condition
CEP41 c.*2389G>A Uncertain significance ★★ same condition
CEP41 p.Ala103Val 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/cep41-p-pro280ala (accessed [today's date]).

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