Is CEP350 p.Pro3015Ser (c.9043C>T) pathogenic?

CEP350 p.Pro3015Ser (c.9043C>T) is classified Uncertain significance in CEP350 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: ambiguous (0.5265); Very rare (popmax 0.000606%, nfe).

How common is CEP350 p.Pro3015Ser (c.9043C>T) in the general population?

CEP350 p.Pro3015Ser (c.9043C>T) is very rare (popmax 0.000606%, nfe) (gnomAD).

What do computational predictors say about CEP350 p.Pro3015Ser (c.9043C>T)?

AlphaMissense predicts ambiguous (score 0.5265) — an in-silico prediction, not a clinical call.

CEP350 p.Pro3015Ser

c.9043C>T · VCV4226283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5265 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000606%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5265	ambiguous
REVEL	0.422	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 57 kb · p 0.012 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.000606% European (non-Finnish) · 7/1,154,914 alleles

Filtering AF 0.000252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000162%

Overall 0.000446% 7/1,568,050 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: CEP350
Protein: p.Pro3015Ser
Coding: c.9043C>T
MANE Select: NM_014810
Type: single nucleotide variant
Location: chr1:180096161 (GRCh38)
Gene constraint: LOEUF 0.402 · pLI 1.00 (gnomAD)

Full CEP350 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP350 p.Asp522Gly Benign ★★ same type
CEP350 p.His1462Arg Likely benign ★★ same type
CEP350 p.Ile1905Met Likely benign ★★ same type
CEP350 p.Lys2735Asn Benign ★★ same type
CEP350 c.5567+1G>A Uncertain significance ★ same type
CEP350 p.Ala1096Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1160Thr Uncertain significance ★ ⚠ same type
CEP350 p.Ala1163Pro 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/cep350-p-pro3015ser (accessed [today's date]).

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