Is CEP152 p.Arg561Cys (c.1681C>T) pathogenic?

CEP152 p.Arg561Cys (c.1681C>T) is classified Uncertain significance in CEP152 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). AlphaMissense: likely benign (0.249); Ultra-rare (popmax 0.0495%, mid).

How common is CEP152 p.Arg561Cys (c.1681C>T) in the general population?

CEP152 p.Arg561Cys (c.1681C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CEP152 p.Arg561Cys (c.1681C>T)?

AlphaMissense predicts likely benign (score 0.249) — an in-silico prediction, not a clinical call.

CEP152 p.Arg561Cys

c.1681C>T · rs1447022316 · VCV1913441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.249 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.249	likely benign
REVEL	0.516	indeterminate
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 5.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	29.5	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 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.000889% 13/1,461,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0032%	31,250
East Asian	0.00223%	44,866
South Asian	0.0011%	91,072
European (non-Finnish)	0.000509%	196,637

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: CEP152
Protein: p.Arg561Cys
Coding: c.1681C>T
MANE Select: NM_001194998
dbSNP: rs1447022316
Type: single nucleotide variant
Location: chr15:48772588 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB

Full CEP152 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP152 c.1578-1G>A Likely pathogenic ★★ same type
CEP152 c.1908+1G>T Likely pathogenic ★★ same type
CEP152 c.540+1G>A Pathogenic/Likely pathogenic ★★ same type
CEP152 c.88-2A>G Likely pathogenic ★★ same type
CEP152 c.972+2T>A Likely pathogenic ★★ same type
CEP152 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
CEP152 p.Arg1309Ter Pathogenic/Likely pathogenic ★★ same type
CEP152 p.Arg267Ter Pathogenic/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/cep152-p-arg561cys (accessed [today's date]).

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