Is GRN p.Ser120= (c.360C>T) pathogenic?

GRN p.Ser120= (c.360C>T) is classified Benign/Likely benign in GRN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-09). Ultra-rare (popmax 0.0454%, afr); Associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions.

How common is GRN p.Ser120= (c.360C>T) in the general population?

GRN p.Ser120= (c.360C>T) is ultra-rare (popmax 0.0454%, afr) (gnomAD).

GRN p.Ser120=

Q: What condition is associated with GRN p.Ser120= (c.360C>T)?

GRN p.Ser120= (c.360C>T) is associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.360C>T · rs375183423 · VCV718836

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0454%, afr)

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.
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -2.8
Overall
CADD	8.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0454% African / African-American · 34/74,832 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0292%

Overall 0.00527% 85/1,611,656 alleles · ultra-rare exomes 53/1,459,600 · genomes 32/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0454%	2,201
East Asian	0.0312%	3,205
Admixed American	0.00667%	14,996
Remaining individualsnot grpmax-eligible	0.00321%	31,197
European (non-Finnish)	0.00255%	39,265
South Asian	0.0011%	91,034

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.Ser120=
Coding: c.360C>T
MANE Select: NM_002087
dbSNP: rs375183423
Type: single nucleotide variant
Location: chr17:44350238 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB
Residue 120: a UniProt-annotated variant site (in)

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

Disease context

Also linked: neuronal ceroid lipofuscinosis 11

Similar variants

GRN p.Ser120Tyr Benign/Likely benign ★★ 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
GRN c.709-2A>G 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-ser120 (accessed [today's date]).

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