Is CEP164 p.Arg34Leu (c.101G>T) pathogenic?

CEP164 p.Arg34Leu (c.101G>T) is classified Uncertain significance in CEP164 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-11). AlphaMissense: ambiguous (0.341); Ultra-rare (popmax 0.0276%, sas); Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Arg34Leu (c.101G>T)?

CEP164 p.Arg34Leu (c.101G>T) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg34Leu (c.101G>T) in the general population?

CEP164 p.Arg34Leu (c.101G>T) is ultra-rare (popmax 0.0276%, sas) (gnomAD).

How is Senior-Loken syndrome inherited?

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

What do computational predictors say about CEP164 p.Arg34Leu (c.101G>T)?

AlphaMissense predicts ambiguous (score 0.341) — an in-silico prediction, not a clinical call.

CEP164 p.Arg34Leu

c.101G>T · rs760829793 · VCV1004967

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.341 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

nephronophthisis 15

Computational evidence

Protein change
AlphaMissense	0.341	ambiguous
REVEL	0.165	moderately benign-leaning
SaProt	LLR -8.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0276% South Asian · 25/90,574 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00155% 25/1,611,374 alleles · ultra-rare

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.Arg34Leu
Coding: c.101G>T
MANE Select: NM_014956
dbSNP: rs760829793
Type: single nucleotide variant
Location: chr11:117344184 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 34: the 'interaction with atrip' region; an α-helix

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.Arg34Gln Uncertain significance ★★ ⚠ same residue
CEP164 p.Arg34Gly Uncertain significance ★★ ⚠ same residue
CEP164 p.Arg34Trp 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-arg34leu (accessed [today's date]).

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