Is GBE1 p.Ala615Pro (c.1843G>C) pathogenic?

GBE1 p.Ala615Pro (c.1843G>C) is classified Likely pathogenic in GBE1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.8893); Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 15.

What condition is associated with GBE1 p.Ala615Pro (c.1843G>C)?

GBE1 p.Ala615Pro (c.1843G>C) is associated with osteogenesis imperfecta type 15 (ClinVar).

How common is GBE1 p.Ala615Pro (c.1843G>C) in the general population?

GBE1 p.Ala615Pro (c.1843G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GBE1 p.Ala615Pro (c.1843G>C)?

AlphaMissense predicts likely pathogenic (score 0.8893) — an in-silico prediction, not a clinical call.

GBE1 p.Ala615Pro

c.1843G>C · rs768485124 · VCV1332751

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

osteogenesis imperfecta type 15

Computational evidence

Protein change
AlphaMissense	0.8893	likely pathogenic ✓ concordant with ClinVar
REVEL	0.514	indeterminate
SaProt	LLR -12.86	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -4.8
Regional constraint	o/e 1.00	unconstrained · MANE · 271 kb · p 0.97 · regional, not allelic
Overall
CADD	17.56	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: GBE1
Protein: p.Ala615Pro
Coding: c.1843G>C
MANE Select: NM_000158
dbSNP: rs768485124
Type: single nucleotide variant
Location: chr3:81535286 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 615: a β-strand

Full GBE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GBE1 p.Ala615Asp Uncertain significance ★ ⚠ same residue
GBE1 c.1109-1G>T Likely pathogenic ★★ same type
GBE1 c.1236+1G>A Likely pathogenic ★★ same type
GBE1 c.1336-1G>A Pathogenic/Likely pathogenic ★★ same type
GBE1 c.143+1G>A Pathogenic ★★ same type
GBE1 c.143+2T>C Pathogenic/Likely pathogenic ★★ same type
GBE1 c.144-1G>C Pathogenic/Likely pathogenic ★★ same type
GBE1 c.1618+1G>A Pathogenic/Likely pathogenic ★★ 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/gbe1-p-ala615pro (accessed [today's date]).

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