Is CEP164 p.Pro339= (c.1017T>C) pathogenic?

CEP164 p.Pro339= (c.1017T>C) is classified Likely benign in CEP164 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.000169%, nfe); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Pro339= (c.1017T>C)?

CEP164 p.Pro339= (c.1017T>C) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Pro339= (c.1017T>C) in the general population?

CEP164 p.Pro339= (c.1017T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Senior-Loken syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CEP164 p.Pro339=

c.1017T>C · rs2541194839 · VCV2815092

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

nephronophthisis 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 0.54	GERP -0.87
Overall
CADD	6.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,028 alleles

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

Overall 0.000124% 2/1,614,184 alleles · very rare exomes 2/1,461,888 · genomes 0/152,296 · joint denominator

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: CEP164
Protein: p.Pro339=
Coding: c.1017T>C
MANE Select: NM_014956
dbSNP: rs2541194839
Type: single nucleotide variant
Location: chr11:117371331 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 339: the 'disordered' region

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CEP164 c.1234-2A>T Likely pathogenic ★★ same condition
CEP164 c.1724+1G>A Likely pathogenic ★★ same condition
CEP164 c.1934+1G>A Likely pathogenic ★★ same condition
CEP164 c.2361+1G>A Likely pathogenic ★★ same condition
CEP164 c.2493+1G>A Likely pathogenic ★★ same condition
CEP164 c.2914-1G>C Likely pathogenic ★★ same condition
CEP164 c.3748+2T>C Likely pathogenic ★★ same condition
CEP164 c.3749-2A>G Likely pathogenic ★★ 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/cep164-p-pro339 (accessed [today's date]).

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