Is CEP164 p.Pro127= (c.381C>A) pathogenic?

CEP164 p.Pro127= (c.381C>A) is classified Likely benign in CEP164 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-03). Ultra-rare (popmax 0.0734%, sas); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Pro127= (c.381C>A)?

CEP164 p.Pro127= (c.381C>A) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Pro127= (c.381C>A) in the general population?

CEP164 p.Pro127= (c.381C>A) is ultra-rare (popmax 0.0734%, sas) (gnomAD).

How is Senior-Loken syndrome inherited?

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

CEP164 p.Pro127=

c.381C>A · rs375951540 · VCV1572267

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, sas)

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 -0.067	GERP -1.6, phastCons 0.002
Overall
CADD	1.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% South Asian · 64/87,250 alleles

Filtering AF 0.0589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0537%

Overall 0.00988% 156/1,578,506 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0734%	1,363
East Asian	0.0255%	3,922
Middle Eastern	0.0167%	5,990
European (non-Finnish)	0.00663%	15,088
Remaining individualsnot grpmax-eligible	0.0049%	20,406

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.Pro127=
Coding: c.381C>A
MANE Select: NM_014956
dbSNP: rs375951540
Type: single nucleotide variant
Location: chr11:117351976 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 127: the 'interaction with atrip' region; 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.Pro127Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP164 p.Pro127His Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP164 p.Pro127Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro127 (accessed [today's date]).

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