Is CEP170 p.Ser1384Pro (c.4150T>C) pathogenic?

CEP170 p.Ser1384Pro (c.4150T>C) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.0655); Very rare (popmax 0.00017%, nfe).

How common is CEP170 p.Ser1384Pro (c.4150T>C) in the general population?

CEP170 p.Ser1384Pro (c.4150T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CEP170 p.Ser1384Pro (c.4150T>C)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

CEP170 p.Ser1384Pro

c.4150T>C · rs2055638884 · VCV3142655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.57	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 0.56, phastCons 0.97
Regional constraint	o/e 0.91	unconstrained · MANE · 2,353 bp · p 0.47 · regional, not allelic
Overall
CADD	16.23	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 0.00017% European (non-Finnish) · 2/1,179,874 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,670 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: CEP170
Protein: p.Ser1384Pro
Coding: c.4150T>C
MANE Select: NM_014812
dbSNP: rs2055638884
Type: single nucleotide variant
Location: chr1:243140017 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.25 · 1 PDB
Residue 1384: the 'disordered' region; the 'targeting to microtubules' region; the 'interaction with ccdc61' 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-ser1384pro (accessed [today's date]).

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