Is GRN p.Asp33fs (c.93_96dup) pathogenic?

GRN p.Asp33fs (c.9396dup) is classified Pathogenic in GRN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-04-01). No gnomAD frequency available for this variant; Associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions.

What condition is associated with GRN p.Asp33fs (c.93_96dup)?

GRN p.Asp33fs (c.93_96dup) is associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions (ClinVar).

How common is GRN p.Asp33fs (c.93_96dup) in the general population?

GRN p.Asp33fs (c.93_96dup) is no gnomAD frequency available for this variant (gnomAD).

GRN p.Asp33fs

c.93_96dup · rs606231220 · VCV16010

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GRN
Protein: p.Asp33fs
Coding: c.93_96dup
MANE Select: NM_002087
dbSNP: rs606231220
Type: Duplication
Location: chr17:44349253 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB

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

Disease context

GRN-related frontotemporal lobar degeneration with Tdp43 inclusions — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRN p.Asp33= Benign/Likely benign ★★ same residue
GRN p.Asp33Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
GRN p.Cys31fs Pathogenic ★★ same condition
GRN p.Lys259Ter Pathogenic ★★ same condition
GRN c.350-50_350-47dup Benign ★★ same condition
GRN p.Cys30fs Pathogenic ★ same condition
GRN p.Cys41Ter Pathogenic ★ same condition
GRN p.Cys61fs Pathogenic ★ 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/grn-p-asp33fs (accessed [today's date]).

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