Is CEP41 p.Arg5Lys (c.14G>A) pathogenic?

CEP41 p.Arg5Lys (c.14G>A) is classified Uncertain significance in CEP41 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.1749); Very rare (popmax 0.000169%, nfe); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Arg5Lys (c.14G>A)?

CEP41 p.Arg5Lys (c.14G>A) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Arg5Lys (c.14G>A) in the general population?

CEP41 p.Arg5Lys (c.14G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CEP41 p.Arg5Lys (c.14G>A)?

AlphaMissense predicts likely benign (score 0.1749) — an in-silico prediction, not a clinical call.

CEP41 p.Arg5Lys

c.14G>A · rs1240057172 · VCV2018329

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1749 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.1749	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,026 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,802 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: CEP41
Protein: p.Arg5Lys
Coding: c.14G>A
MANE Select: NM_018718
dbSNP: rs1240057172
Type: single nucleotide variant
Location: chr7:130440953 (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 p.Arg5Gly Uncertain significance ★ ⚠ 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
CEP41 c.*2389G>A 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-arg5lys (accessed [today's date]).

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