Is CEP170 p.Pro846Ser (c.2536C>T) pathogenic?

CEP170 p.Pro846Ser (c.2536C>T) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely benign (0.0829); Very rare (popmax 0.0041%, afr).

How common is CEP170 p.Pro846Ser (c.2536C>T) in the general population?

CEP170 p.Pro846Ser (c.2536C>T) is very rare (popmax 0.0041%, afr) (gnomAD).

What do computational predictors say about CEP170 p.Pro846Ser (c.2536C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

CEP170 p.Pro846Ser

c.2536C>T · rs750149131 · VCV2266720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0041%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.40	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 4.1	GERP 2.2, phastCons 1
Regional constraint	o/e 0.19	constrained · MANE · 216 bp · p 1.8e-13 · regional, not allelic
Overall
CADD	15.17	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 0.0041% African / African-American · 3/73,178 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.00019% 3/1,579,070 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.Pro846Ser
Coding: c.2536C>T
MANE Select: NM_014812
dbSNP: rs750149131
Type: single nucleotide variant
Location: chr1:243165424 (GRCh38)
Gene constraint: LOEUF 0.261 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.25 · 1 PDB
Residue 846: the 'disordered' 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-pro846ser (accessed [today's date]).

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