Is GRN p.Ser383= (c.1149T>A) pathogenic?

GRN p.Ser383= (c.1149T>A) is classified Likely benign in GRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). Absent from gnomAD v4.1; Associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions.

How common is GRN p.Ser383= (c.1149T>A) in the general population?

GRN p.Ser383= (c.1149T>A) is absent from gnomAD v4.1 (gnomAD).

GRN p.Ser383=

Q: What condition is associated with GRN p.Ser383= (c.1149T>A)?

GRN p.Ser383= (c.1149T>A) is associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.1149T>A · rs2510057419 · VCV2938949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.3	GERP 1.5, phastCons 0.001
Overall
CADD	3.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRN
Protein: p.Ser383=
Coding: c.1149T>A
MANE Select: NM_002087
dbSNP: rs2510057419
Type: single nucleotide variant
Location: chr17:44351765 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB
Residue 383: a β-strand

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 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
GRN c.934-1G>A Likely 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-ser383 (accessed [today's date]).

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