Is GRN p.Ser301= (c.903G>A) pathogenic?

GRN p.Ser301= (c.903G>A) is classified Benign/Likely benign in GRN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-17). Rare (popmax 0.102%, nfe); Associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions.

How common is GRN p.Ser301= (c.903G>A) in the general population?

GRN p.Ser301= (c.903G>A) is rare (popmax 0.102%, nfe) (gnomAD).

GRN p.Ser301=

Q: What condition is associated with GRN p.Ser301= (c.903G>A)?

GRN p.Ser301= (c.903G>A) is associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.903G>A · rs63750142 · VCV98159

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, nfe)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.1
Overall
CADD	2.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% European (non-Finnish) · 1,206/1,179,526 alleles

Filtering AF 0.0974% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0955%

Overall 0.0811% 1,309/1,613,512 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.102%	978
Middle Eastern	0.0991%	1,009
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Finnishnot grpmax-eligible	0.0375%	2,666
African / African-American	0.0213%	4,687
South Asian	0.011%	9,106
Admixed American	0.00833%	12,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Ser301=
Coding: c.903G>A
MANE Select: NM_002087
dbSNP: rs63750142
Type: single nucleotide variant
Location: chr17:44351430 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB
Residue 301: a disulfide bond

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.Ser301Leu 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
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-ser301 (accessed [today's date]).

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