Is CEP152 p.Ser590Arg (c.1770C>A) pathogenic?

CEP152 p.Ser590Arg (c.1770C>A) is classified Uncertain significance in CEP152 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-23). AlphaMissense: likely benign (0.2239); Ultra-rare (popmax 0.0557%, eas); Associated with Inborn genetic diseases.

What condition is associated with CEP152 p.Ser590Arg (c.1770C>A)?

CEP152 p.Ser590Arg (c.1770C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEP152 p.Ser590Arg (c.1770C>A) in the general population?

CEP152 p.Ser590Arg (c.1770C>A) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

What do computational predictors say about CEP152 p.Ser590Arg (c.1770C>A)?

AlphaMissense predicts likely benign (score 0.2239) — an in-silico prediction, not a clinical call.

CEP152 p.Ser590Arg

c.1770C>A · rs774531213 · VCV1930347

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2239 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2239	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -6.25	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 3	GERP 3.4, phastCons 0.24
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.21 · regional, not allelic
Overall
CADD	15.7	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 0.0557% East Asian · 25/44,880 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00161% 26/1,612,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,795
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Ser590Arg
Coding: c.1770C>A
MANE Select: NM_001194998
dbSNP: rs774531213
Type: single nucleotide variant
Location: chr15:48772499 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.54 · 3 PDB
Residue 590: the 'disordered' region

Full CEP152 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

Similar variants

CEP152 p.Ser590Asn Uncertain significance ★ ⚠ same residue
CEP152 p.Ser590Gly Uncertain significance ★ ⚠ same residue
CEP152 c.540+6G>A Uncertain significance ★★ same condition
CEP152 p.Ala165Gly Uncertain significance ★★ ⚠ same condition
CEP152 p.Ala411Thr Uncertain significance ★★ ⚠ same condition
CEP152 p.Ala956Val Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1034Gln Uncertain significance ★★ ⚠ same condition
CEP152 p.Arg1283Cys Uncertain significance ★★ ⚠ 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/cep152-p-ser590arg (accessed [today's date]).

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