Is CEP164 p.Pro334Arg (c.1001C>G) pathogenic?

CEP164 p.Pro334Arg (c.1001C>G) is classified Uncertain significance in CEP164 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0836); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP164 p.Pro334Arg (c.1001C>G)?

CEP164 p.Pro334Arg (c.1001C>G) is associated with Inborn genetic diseases, nephronophthisis 15 (ClinVar).

How common is CEP164 p.Pro334Arg (c.1001C>G) in the general population?

CEP164 p.Pro334Arg (c.1001C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CEP164 p.Pro334Arg (c.1001C>G)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

CEP164 p.Pro334Arg

c.1001C>G · rs2042173742 · VCV941564

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.65, phastCons 0.001
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	13.01	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

Grpmax group 0.00333% Admixed American · 2/60,010 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000248% 4/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,938

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.Pro334Arg
Coding: c.1001C>G
MANE Select: NM_014956
dbSNP: rs2042173742
Type: single nucleotide variant
Location: chr11:117371315 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 334: the 'disordered' region

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.Pro334_Thr335insLysAlaAspPro 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-pro334arg (accessed [today's date]).

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