Is CEP170 p.Ser309Pro (c.925T>C) pathogenic?

CEP170 p.Ser309Pro (c.925T>C) is classified Uncertain significance in CEP170 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0751); Ultra-rare (popmax 0.0494%, mid).

How common is CEP170 p.Ser309Pro (c.925T>C) in the general population?

CEP170 p.Ser309Pro (c.925T>C) is ultra-rare (popmax 0.0494%, mid) (gnomAD).

What do computational predictors say about CEP170 p.Ser309Pro (c.925T>C)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

CEP170 p.Ser309Pro

c.925T>C · rs372623014 · VCV3142660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.83	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 6.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 118 bp · p 7.2e-06 · regional, not allelic
Overall
CADD	20.4	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 0.0494% Middle Eastern · 3/6,078 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00894% 144/1,610,778 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0494%	2,026
Remaining individualsnot grpmax-eligible	0.0192%	5,199
European (non-Finnish)	0.0102%	9,820
African / African-American	0.00669%	14,940
Admixed American	0.00336%	29,785
South Asian	0.00221%	45,275

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.Ser309Pro
Coding: c.925T>C
MANE Select: NM_014812
dbSNP: rs372623014
Type: single nucleotide variant
Location: chr1:243191201 (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-ser309pro (accessed [today's date]).

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