Is CEP41 p.Pro206Ala (c.616C>G) pathogenic?

CEP41 p.Pro206Ala (c.616C>G) is classified Conflicting classifications of pathogenicity in CEP41 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.5991); Rare (popmax 0.382%, nfe); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Pro206Ala (c.616C>G)?

CEP41 p.Pro206Ala (c.616C>G) is associated with Joubert syndrome 15, intellectual disability (ClinVar).

How common is CEP41 p.Pro206Ala (c.616C>G) in the general population?

CEP41 p.Pro206Ala (c.616C>G) is rare (popmax 0.382%, nfe) (gnomAD).

What do computational predictors say about CEP41 p.Pro206Ala (c.616C>G)?

AlphaMissense predicts likely pathogenic (score 0.5991) — an in-silico prediction, not a clinical call.

CEP41 p.Pro206Ala

c.616C>G · rs143303575 · VCV358942

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely pathogenic

0.5991 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.382%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 15

Computational evidence

Protein change
AlphaMissense	0.5991	likely pathogenic
REVEL	0.203	benign-leaning
SaProt	LLR -9.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 42 kb · p 0.28 · regional, not allelic
Overall
CADD	29.7	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 0.382% European (non-Finnish) · 4,493/1,175,152 alleles

Filtering AF 0.373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.369%

Overall 0.319% 5,136/1,608,600 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.382%	262
Remaining individualsnot grpmax-eligible	0.358%	279
Finnishnot grpmax-eligible	0.322%	311
South Asian	0.154%	649
Admixed American	0.0534%	1,874
African / African-American	0.0507%	1,971
Middle Eastern	0.0496%	2,017
East Asian	0.00223%	44,840

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.Pro206Ala
Coding: c.616C>G
MANE Select: NM_018718
dbSNP: rs143303575
Type: single nucleotide variant
Location: chr7:130401907 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 206: the rhodanese domain; a UniProt-annotated variant site (found in a patient with autism; uncertain significance)

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

Also linked: intellectual disability

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-pro206ala (accessed [today's date]).

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