Is CEP164 p.Arg1417Trp (c.4249C>T) pathogenic?

CEP164 p.Arg1417Trp (c.4249C>T) is classified Uncertain significance in CEP164 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-08). AlphaMissense: likely benign (0.2494); Ultra-rare (popmax 0.045%, sas); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Arg1417Trp (c.4249C>T)?

CEP164 p.Arg1417Trp (c.4249C>T) is associated with Inborn genetic diseases, nephronophthisis 15 (ClinVar).

How common is CEP164 p.Arg1417Trp (c.4249C>T) in the general population?

CEP164 p.Arg1417Trp (c.4249C>T) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about CEP164 p.Arg1417Trp (c.4249C>T)?

AlphaMissense predicts likely benign (score 0.2494) — an in-silico prediction, not a clinical call.

CEP164 p.Arg1417Trp

c.4249C>T · rs745904143 · VCV1493642

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2494 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2494	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -11.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	24.0	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 0.045% South Asian · 41/91,070 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00483% 78/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,221
Admixed American	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00237%	42,144
African / African-American	0.00133%	74,914

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.Arg1417Trp
Coding: c.4249C>T
MANE Select: NM_014956
dbSNP: rs745904143
Type: single nucleotide variant
Location: chr11:117411880 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 15

Similar variants

CEP164 p.Arg1417Pro Uncertain significance ★★ ⚠ same residue
CEP164 p.Arg1417Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CEP164 p.Arg1417Gly Uncertain significance ★ ⚠ same residue
CEP164 p.Arg1417= Likely benign ★ 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

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-arg1417trp (accessed [today's date]).

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