Is CEP41 p.Ser337Pro (c.1009T>C) pathogenic?

CEP41 p.Ser337Pro (c.1009T>C) is classified Conflicting classifications of pathogenicity in CEP41 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.0946); Rare (popmax 0.728%, afr); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Ser337Pro (c.1009T>C)?

CEP41 p.Ser337Pro (c.1009T>C) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Ser337Pro (c.1009T>C) in the general population?

CEP41 p.Ser337Pro (c.1009T>C) is rare (popmax 0.728%, afr) (gnomAD).

What do computational predictors say about CEP41 p.Ser337Pro (c.1009T>C)?

AlphaMissense predicts likely benign (score 0.0946) — an in-silico prediction, not a clinical call.

CEP41 p.Ser337Pro

c.1009T>C · rs147444165 · VCV358939

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0946 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.728%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.0946	likely benign
REVEL	0.264	benign-leaning
SaProt	LLR -6.43	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 2.5	GERP -2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	17.97	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 0.728% African / African-American · 546/75,016 alleles

Filtering AF 0.677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.657%

Overall 0.0426% 687/1,614,066 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.728%	137
Middle Eastern	0.116%	866
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Admixed American	0.08%	1,250
South Asian	0.00659%	15,180
European (non-Finnish)	0.0022%	45,385

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.Ser337Pro
Coding: c.1009T>C
MANE Select: NM_018718
dbSNP: rs147444165
Type: single nucleotide variant
Location: chr7:130399004 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 337: 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-ser337pro (accessed [today's date]).

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