Is CEP164 p.Ser735= (c.2205C>T) pathogenic?

CEP164 p.Ser735= (c.2205C>T) is classified Benign/Likely benign in CEP164 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 5.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Ser735= (c.2205C>T)?

CEP164 p.Ser735= (c.2205C>T) 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.Ser735=

Q: How common is CEP164 p.Ser735= (c.2205C>T) in the general population?

CEP164 p.Ser735= (c.2205C>T) is common (popmax 5.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2205C>T · rs494553 · VCV260478

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.6%, nfe) — 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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Constraint at this position
Conservation	phyloP -2.7	GERP -2.8
Overall
CADD	9.149	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.6% European (non-Finnish) · 66,062/1,179,942 alleles

Filtering AF 5.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.55%

Overall 4.79% 77,222/1,613,770 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	17.3%	6
Ashkenazi Jewishnot grpmax-eligible	6.62%	15
European (non-Finnish)grpmax	5.6%	18
Remaining individualsnot grpmax-eligible	4.67%	21
Middle Eastern	4%	25
Finnishnot grpmax-eligible	3.6%	28
Admixed American	2.43%	41
South Asian	1.69%	59
African / African-American	0.779%	128
East Asian	0.0201%	4,981

Amish 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: CEP164
Protein: p.Ser735=
Coding: c.2205C>T
MANE Select: NM_014956
dbSNP: rs494553
Type: single nucleotide variant
Location: chr11:117391137 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB

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-ser735 (accessed [today's date]).

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