Is CEP164 p.Arg1249Ser (c.3747G>T) pathogenic?

CEP164 p.Arg1249Ser (c.3747G>T) is classified Uncertain significance in CEP164 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.1379); Absent from gnomAD v4.1; Associated with nephronophthisis 15.

What condition is associated with CEP164 p.Arg1249Ser (c.3747G>T)?

CEP164 p.Arg1249Ser (c.3747G>T) is associated with nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg1249Ser (c.3747G>T) in the general population?

CEP164 p.Arg1249Ser (c.3747G>T) is absent from gnomAD v4.1 (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.Arg1249Ser (c.3747G>T)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

CEP164 p.Arg1249Ser

c.3747G>T · rs1458226426 · VCV1002704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephronophthisis 15

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.41	GERP -2.3, phastCons 0.012
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	2.524	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP164
Protein: p.Arg1249Ser
Coding: c.3747G>T
MANE Select: NM_014956
dbSNP: rs1458226426
Type: single nucleotide variant
Location: chr11:117409027 (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 p.Arg1249Gly 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
CEP164 c.2914-1G>C Likely pathogenic ★★ same condition
CEP164 c.3748+2T>C 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-arg1249ser (accessed [today's date]).

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