Is GRN p.Cys92= (c.276C>T) pathogenic?

GRN p.Cys92= (c.276C>T) is classified Likely benign in GRN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0628%, afr); Associated with Inborn genetic diseases.

How common is GRN p.Cys92= (c.276C>T) in the general population?

GRN p.Cys92= (c.276C>T) is ultra-rare (popmax 0.0628%, afr) (gnomAD).

GRN p.Cys92=

Q: What condition is associated with GRN p.Cys92= (c.276C>T)?

GRN p.Cys92= (c.276C>T) is associated with Inborn genetic diseases, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.276C>T · rs146792371 · VCV1215483

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0628%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.2	GERP -2.4
Overall
CADD	3.867	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0628% African / African-American · 47/74,900 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00924% 149/1,611,932 alleles · ultra-rare exomes 112/1,459,678 · genomes 37/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0628%	1,594
Middle Eastern	0.0164%	6,082
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.00801%	12,484
European (non-Finnish)	0.00721%	13,861
South Asian	0.0022%	45,530

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.Cys92=
Coding: c.276C>T
MANE Select: NM_002087
dbSNP: rs146792371
Type: single nucleotide variant
Location: chr17:44349678 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GRN-related frontotemporal lobar degeneration with Tdp43 inclusions neuronal ceroid lipofuscinosis 11

Similar variants

GRN p.Cys92Arg 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-cys92 (accessed [today's date]).

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