Is CEP164 p.Pro494= (c.1482T>C) pathogenic?

CEP164 p.Pro494= (c.1482T>C) is classified Benign/Likely benign in CEP164 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 95.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Pro494= (c.1482T>C)?

CEP164 p.Pro494= (c.1482T>C) is associated with nephronophthisis 15 (ClinVar).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Pro494=

Q: How common is CEP164 p.Pro494= (c.1482T>C) in the general population?

CEP164 p.Pro494= (c.1482T>C) is common (popmax 95.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1482T>C · rs897836 · VCV260475

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 95.5%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.46	GERP -2.8
Overall
CADD	1.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 95.5% African / African-American · 71,390/74,748 alleles

Filtering AF 94.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 94.7%

Overall 92.8% 1,486,265/1,600,984 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	95.5%	1
Finnishnot grpmax-eligible	95.3%	1
European (non-Finnish)	93.6%	1
Remaining individualsnot grpmax-eligible	92.2%	1
Middle Eastern	90.5%	1
Ashkenazi Jewishnot grpmax-eligible	88.7%	1
Admixed American	87.9%	1
East Asian	86.6%	1
South Asian	86.5%	1
Amishnot grpmax-eligible	85.2%	1

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.Pro494=
Coding: c.1482T>C
MANE Select: NM_014956
dbSNP: rs897836
Type: single nucleotide variant
Location: chr11:117381773 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 494: 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 p.Pro494Thr Benign ★★ same residue
CEP164 p.Pro494Arg Uncertain significance ★ ⚠ same residue
CEP164 p.Pro494Ser Uncertain significance ★ ⚠ same residue
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

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-pro494 (accessed [today's date]).

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