Is GRN p.Ser262Pro (c.784T>C) pathogenic?

GRN p.Ser262Pro (c.784T>C) is classified Uncertain significance in GRN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-06). AlphaMissense: likely benign (0.1198); Absent from gnomAD v4.1; Associated with neuronal ceroid lipofuscinosis 11.

What condition is associated with GRN p.Ser262Pro (c.784T>C)?

GRN p.Ser262Pro (c.784T>C) is associated with neuronal ceroid lipofuscinosis 11, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions (ClinVar).

How common is GRN p.Ser262Pro (c.784T>C) in the general population?

GRN p.Ser262Pro (c.784T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRN p.Ser262Pro (c.784T>C)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

GRN p.Ser262Pro

c.784T>C · rs2048369666 · VCV2421214

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuronal ceroid lipofuscinosis 11

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.573	indeterminate
SaProt	LLR -15.38	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.61, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 2,212 bp · p 0.62 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ser262Pro
Coding: c.784T>C
MANE Select: NM_002087
dbSNP: rs2048369666
Type: single nucleotide variant
Location: chr17:44351112 (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

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.Ser262fs 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-ser262pro (accessed [today's date]).

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