Is CEP164 p.Arg151Pro (c.452G>C) pathogenic?

CEP164 p.Arg151Pro (c.452G>C) is classified Uncertain significance in CEP164 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-29). AlphaMissense: likely pathogenic (0.5842); Very rare (popmax 0.00144%, nfe).

How common is CEP164 p.Arg151Pro (c.452G>C) in the general population?

CEP164 p.Arg151Pro (c.452G>C) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about CEP164 p.Arg151Pro (c.452G>C)?

AlphaMissense predicts likely pathogenic (score 0.5842) — an in-silico prediction, not a clinical call.

CEP164 p.Arg151Pro

c.452G>C · VCV4914111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5842	likely pathogenic · top 9% in CEP164
REVEL	0.344	indeterminate
SaProt	LLR -4.90	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.61	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 74 kb · p 0.19 · regional, not allelic
Overall
CADD	34.0	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 0.00144% European (non-Finnish) · 17/1,180,012 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00116% 17/1,461,814 alleles · very 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.Arg151Pro
Coding: c.452G>C
MANE Select: NM_014956
Type: single nucleotide variant
Location: chr11:117361893 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.08 · 4 PDB
Residue 151: the 'interaction with atrip' region

Full CEP164 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP164 p.Arg151Ter Pathogenic/Likely pathogenic ★★ same residue
CEP164 p.Arg151Gln Uncertain significance ★ ⚠ same residue
CEP164 c.1234-2A>T Likely pathogenic ★★ same type
CEP164 c.1724+1G>A Likely pathogenic ★★ same type
CEP164 c.1934+1G>A Likely pathogenic ★★ same type
CEP164 c.2361+1G>A Likely pathogenic ★★ same type
CEP164 c.2493+1G>A Likely pathogenic ★★ same type
CEP164 c.2914-1G>C Likely pathogenic ★★ same type

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-arg151pro (accessed [today's date]).

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