Is CEP41 p.Arg360Cys (c.1078C>T) pathogenic?

CEP41 p.Arg360Cys (c.1078C>T) is classified Uncertain significance in CEP41 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1096); Ultra-rare (popmax 0.029%, eas); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Arg360Cys (c.1078C>T)?

CEP41 p.Arg360Cys (c.1078C>T) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Arg360Cys (c.1078C>T) in the general population?

CEP41 p.Arg360Cys (c.1078C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about CEP41 p.Arg360Cys (c.1078C>T)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

CEP41 p.Arg360Cys

c.1078C>T · rs371812716 · VCV30843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	32.0	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 0.029% East Asian · 13/44,888 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00273% 44/1,614,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,453
African / African-American	0.00799%	12,509
Admixed American	0.00666%	15,009
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00153%	65,558
South Asian	0.0011%	91,082

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: CEP41
Protein: p.Arg360Cys
Coding: c.1078C>T
MANE Select: NM_018718
dbSNP: rs371812716
Type: single nucleotide variant
Location: chr7:130398935 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 360: a UniProt-annotated variant site (found in a patient with joubert syndrome; likely pathogenic; digenic inheritance; the patient also carries mutation a-1447 in cc2d2a); 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 p.Arg360Pro Uncertain significance ★ ⚠ same residue
CEP41 p.Arg360= Likely benign ★ same residue
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

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-arg360cys (accessed [today's date]).

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