Is GRN p.Cys171= (c.513C>T) pathogenic?

GRN p.Cys171= (c.513C>T) is classified Likely benign in GRN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). Rare (popmax 0.156%, afr); Associated with Inborn genetic diseases.

How common is GRN p.Cys171= (c.513C>T) in the general population?

GRN p.Cys171= (c.513C>T) is rare (popmax 0.156%, afr) (gnomAD).

GRN p.Cys171=

Q: What condition is associated with GRN p.Cys171= (c.513C>T)?

GRN p.Cys171= (c.513C>T) is associated with Inborn genetic diseases, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.513C>T · rs147974849 · VCV473064

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.156%, afr)

Conditions

Inborn genetic diseases

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 -0.078	GERP -2.8, phastCons 0.86
Overall
CADD	9.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.156% African / African-American · 117/75,000 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0114% 184/1,613,900 alleles · rare exomes 122/1,461,682 · genomes 62/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.156%	641
Remaining individualsnot grpmax-eligible	0.0096%	10,417
Admixed American	0.005%	20,002
European (non-Finnish)	0.00483%	20,700
East Asian	0.00223%	44,876

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.Cys171=
Coding: c.513C>T
MANE Select: NM_002087
dbSNP: rs147974849
Type: single nucleotide variant
Location: chr17:44350492 (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 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-cys171 (accessed [today's date]).

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