Is CEP170 p.Ser1529Arg (c.4587C>G) pathogenic?

CEP170 p.Ser1529Arg (c.4587C>G) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.3224); Absent from gnomAD v4.1.

How common is CEP170 p.Ser1529Arg (c.4587C>G) in the general population?

CEP170 p.Ser1529Arg (c.4587C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP170 p.Ser1529Arg (c.4587C>G)?

AlphaMissense predicts likely benign (score 0.3224) — an in-silico prediction, not a clinical call.

CEP170 p.Ser1529Arg

c.4587C>G · rs2053725846 · VCV2484248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3224 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3224	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.62	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 5.2	GERP 0.51, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 239 bp · p 5.3e-05 · regional, not allelic
Overall
CADD	16.93	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CEP170
Protein: p.Ser1529Arg
Coding: c.4587C>G
MANE Select: NM_014812
dbSNP: rs2053725846
Type: single nucleotide variant
Location: chr1:243126617 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.25 · 1 PDB
Residue 1529: the 'disordered' region; the 'targeting to microtubules' region; the 'targeting to centrosomes' region

Full CEP170 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP170 p.Val1524Met Uncertain significance ★★ ⚠ same type
CEP170 c.4319+9A>T Benign ★★ same type
CEP170 p.Met1275Val Benign ★★ same type
CEP170 p.Tyr1291= Benign/Likely benign ★★ same type
CEP170 c.195+1G>A Uncertain significance ★ same type
CEP170 p.Ala1163Val Uncertain significance ★ ⚠ same type
CEP170 p.Ala1310Thr Uncertain significance ★ ⚠ same type
CEP170 p.Ala1392Gly Uncertain significance ★ ⚠ 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/cep170-p-ser1529arg (accessed [today's date]).

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