Is GBE1 p.Asp67Val (c.200A>T) pathogenic?

GBE1 p.Asp67Val (c.200A>T) is classified Uncertain significance in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.1689); Very rare (popmax 0.00617%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GBE1 p.Asp67Val (c.200A>T)?

GBE1 p.Asp67Val (c.200A>T) is associated with Inborn genetic diseases (ClinVar).

How common is GBE1 p.Asp67Val (c.200A>T) in the general population?

GBE1 p.Asp67Val (c.200A>T) is very rare (popmax 0.00617%, nfe) (gnomAD).

What do computational predictors say about GBE1 p.Asp67Val (c.200A>T)?

AlphaMissense predicts likely benign (score 0.1689) — an in-silico prediction, not a clinical call.

GBE1 p.Asp67Val

c.200A>T · VCV4262264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00617%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1689	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 271 kb · p 0.97 · regional, not allelic
Overall
CADD	24.1	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 0.00617% European (non-Finnish) · 72/1,166,902 alleles

Filtering AF 0.005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0046%

Overall 0.00465% 74/1,589,928 alleles · very rare exomes 73/1,437,696 · genomes 1/152,232 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00617%	16,207
Remaining individualsnot grpmax-eligible	0.00162%	61,612
African / African-American	0.00134%	74,556

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: GBE1
Protein: p.Asp67Val
Coding: c.200A>T
MANE Select: NM_000158
Type: single nucleotide variant
Location: chr3:81705557 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 67: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GBE1 p.Asp67Gly Uncertain significance ★★ ⚠ same residue
GBE1 p.Glu333Val Pathogenic/Likely pathogenic ★★ same condition
GBE1 p.Arg195Gln Uncertain significance ★★ ⚠ same condition
GBE1 p.Asp586Gly Uncertain significance ★★ ⚠ same condition
GBE1 p.Glu591Lys Uncertain significance ★★ ⚠ same condition
GBE1 p.Gly429Ala Uncertain significance ★★ ⚠ same condition
GBE1 p.Gly65Ser Uncertain significance ★★ ⚠ same condition
GBE1 p.Ile153Asn Uncertain significance ★★ ⚠ same condition

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-asp67val (accessed [today's date]).

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