Is CEP41 p.Pro172= (c.516C>T) pathogenic?

CEP41 p.Pro172= (c.516C>T) is classified Likely benign in CEP41 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). Very rare (popmax 0.00136%, nfe); Associated with Joubert syndrome 15.

What condition is associated with CEP41 p.Pro172= (c.516C>T)?

CEP41 p.Pro172= (c.516C>T) is associated with Joubert syndrome 15 (ClinVar).

How common is CEP41 p.Pro172= (c.516C>T) in the general population?

CEP41 p.Pro172= (c.516C>T) is very rare (popmax 0.00136%, nfe) (gnomAD).

CEP41 p.Pro172=

c.516C>T · VCV4803356

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

Joubert syndrome 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,180,010 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00123% 18/1,461,860 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)grpmax	0.00136%	73,751
South Asian	0.0011%	91,076

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro172=
Coding: c.516C>T
MANE Select: NM_018718
Type: single nucleotide variant
Location: chr7:130402706 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.06 · 1 PDB
Residue 172: the rhodanese domain

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.Pro172Ser 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-pro172 (accessed [today's date]).

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