Is CEP41 p.Ala345Ser (c.1033G>T) pathogenic?

CEP41 p.Ala345Ser (c.1033G>T) is classified Conflicting classifications of pathogenicity in CEP41 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-15). AlphaMissense: likely benign (0.0649); Very rare (popmax 0.00881%, nfe); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Ala345Ser (c.1033G>T)?

CEP41 p.Ala345Ser (c.1033G>T) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Ala345Ser (c.1033G>T) in the general population?

CEP41 p.Ala345Ser (c.1033G>T) is very rare (popmax 0.00881%, nfe) (gnomAD).

What do computational predictors say about CEP41 p.Ala345Ser (c.1033G>T)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

CEP41 p.Ala345Ser

c.1033G>T · rs184146463 · VCV950540

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -5.75	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 -10	GERP -4.9
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	0.003	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 0.00881% European (non-Finnish) · 104/1,180,040 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00663% 107/1,614,186 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00881%	11,347
Admixed American	0.00333%	30,016
African / African-American	0.00133%	75,060

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.Ala345Ser
Coding: c.1033G>T
MANE Select: NM_018718
dbSNP: rs184146463
Type: single nucleotide variant
Location: chr7:130398980 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 345: 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.Ala345Thr Conflicting classifications of pathogenicity ★ ⚠ 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-ala345ser (accessed [today's date]).

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