Is GRN p.Ala9fs (c.25del) pathogenic?

GRN p.Ala9fs (c.25del) is classified Pathogenic in GRN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-01). No gnomAD frequency available for this variant.

How common is GRN p.Ala9fs (c.25del) in the general population?

GRN p.Ala9fs (c.25del) is no gnomAD frequency available for this variant (gnomAD).

GRN p.Ala9fs

c.25del · rs2048347685 · VCV996781

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1.5	GERP 1.2, 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.Ala9fs
Coding: c.25del
MANE Select: NM_002087
dbSNP: rs2048347685
Type: Deletion
Location: chr17:44349188 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB
Residue 9: a UniProt-annotated variant site (in ftd2; no significant difference in the total mrna between cases and controls; although the mutant protein is expressed it is not secreted and appears to be trapped within an intracellular compartment)

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

Similar variants

GRN p.Ala9Asp Pathogenic ★★ same residue
GRN p.Ala9Thr Uncertain significance ★ ⚠ same residue
GRN p.Ala9Val Uncertain significance ★ ⚠ same residue
GRN p.Arg198fs Pathogenic ★★ same type
GRN p.Asp128fs Pathogenic/Likely pathogenic ★★ same type
GRN p.Cys157fs Pathogenic ★★ same type
GRN p.Gln130fs Pathogenic ★★ same type
GRN p.Gln337fs 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/grn-p-ala9fs (accessed [today's date]).

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