Is CEP170 p.Pro289Thr (c.865C>A) pathogenic?

CEP170 p.Pro289Thr (c.865C>A) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). AlphaMissense: ambiguous (0.4356); Absent from gnomAD v4.1.

How common is CEP170 p.Pro289Thr (c.865C>A) in the general population?

CEP170 p.Pro289Thr (c.865C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP170 p.Pro289Thr (c.865C>A)?

AlphaMissense predicts ambiguous (score 0.4356) — an in-silico prediction, not a clinical call.

CEP170 p.Pro289Thr

c.865C>A · rs2547089924 · VCV3142659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4356 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4356	ambiguous
REVEL	0.332	indeterminate
SaProt	LLR -6.09	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 118 bp · p 7.2e-06 · regional, not allelic
Overall
CADD	24.1	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

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.Pro289Thr
Coding: c.865C>A
MANE Select: NM_014812
dbSNP: rs2547089924
Type: single nucleotide variant
Location: chr1:243191261 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.25 · 1 PDB

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-pro289thr (accessed [today's date]).

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