Is GRN p.Ser116= (c.348A>C) pathogenic?

GRN p.Ser116= (c.348A>C) is classified Uncertain significance in GRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). Absent from gnomAD v4.1; Associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions.

How common is GRN p.Ser116= (c.348A>C) in the general population?

GRN p.Ser116= (c.348A>C) is absent from gnomAD v4.1 (gnomAD).

GRN p.Ser116=

Q: What condition is associated with GRN p.Ser116= (c.348A>C)?

GRN p.Ser116= (c.348A>C) is associated with GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.348A>C · rs2510054792 · VCV2925623

Uncertain significance Single submitter

Classification

Uncertain significance

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/SpliceAI carries the signal.
REVEL	0.179	moderately benign-leaning
Splicing
SpliceAI	Δ0.59	donor loss · deltas
Pangolin	Δ0.57	loss · gain 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 0.24, phastCons 1
Overall
CADD	19.2	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.Ser116=
Coding: c.348A>C
MANE Select: NM_002087
dbSNP: rs2510054792
Type: single nucleotide variant
Location: chr17:44349750 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB

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.Ser116Ter Pathogenic ★ 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-ser116 (accessed [today's date]).

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