Is GRN p.Arg19= (c.57G>T) pathogenic?

GRN p.Arg19= (c.57G>T) is classified Conflicting classifications of pathogenicity in GRN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-04-12). Ultra-rare (popmax 0.029%, eas); Associated with neuronal ceroid lipofuscinosis 11.

What condition is associated with GRN p.Arg19= (c.57G>T)?

GRN p.Arg19= (c.57G>T) is associated with neuronal ceroid lipofuscinosis 11, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions (ClinVar).

How common is GRN p.Arg19= (c.57G>T) in the general population?

GRN p.Arg19= (c.57G>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

GRN p.Arg19=

c.57G>T · rs1426790644 · VCV890386

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

neuronal ceroid lipofuscinosis 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.15, phastCons 0.99
Overall
CADD	6.747	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,902 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.000805% 13/1,613,940 alleles · ultra-rare exomes 9/1,461,690 · genomes 4/152,250 · joint denominator

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: GRN
Protein: p.Arg19=
Coding: c.57G>T
MANE Select: NM_002087
dbSNP: rs1426790644
Type: single nucleotide variant
Location: chr17:44349221 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB
Residue 19: a UniProt-annotated variant site (in)

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

Disease context

neuronal ceroid lipofuscinosis 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GRN-related frontotemporal lobar degeneration with Tdp43 inclusions

For CLN11 disease (Orphanet):

Onset: Adolescent, Infancy

Similar variants

GRN p.Arg19Trp Benign ★★ same residue
GRN p.Arg19Gln Uncertain significance ★ ⚠ same residue
GRN c.1414-1G>T Pathogenic ★★ same condition
GRN c.1414-2A>G Pathogenic ★★ same condition
GRN c.264+1G>A Likely pathogenic ★★ same condition
GRN c.349+1G>C Pathogenic ★★ same condition
GRN c.599-1G>A Pathogenic/Likely pathogenic ★★ same condition
GRN c.709-1G>A 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-arg19 (accessed [today's date]).

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