Is CEP41 p.Pro167Ser (c.499C>T) pathogenic?

CEP41 p.Pro167Ser (c.499C>T) is classified Uncertain significance in CEP41 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely pathogenic (0.74); Absent from gnomAD v4.1; Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Pro167Ser (c.499C>T)?

CEP41 p.Pro167Ser (c.499C>T) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Pro167Ser (c.499C>T) in the general population?

CEP41 p.Pro167Ser (c.499C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP41 p.Pro167Ser (c.499C>T)?

AlphaMissense predicts likely pathogenic (score 0.74) — an in-silico prediction, not a clinical call.

CEP41 p.Pro167Ser

c.499C>T · rs1796890244 · VCV1516904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.74 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.74	likely pathogenic
REVEL	0.727	pathogenic-leaning
SaProt	LLR -3.60	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	28.1	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

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.Pro167Ser
Coding: c.499C>T
MANE Select: NM_018718
dbSNP: rs1796890244
Type: single nucleotide variant
Location: chr7:130402723 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB

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-pro167ser (accessed [today's date]).

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