Is GRN p.Ala505= (c.1515C>T) pathogenic?

GRN p.Ala505= (c.1515C>T) is classified Likely benign in GRN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-01). Rare (popmax 0.131%, afr); Associated with Inborn genetic diseases.

How common is GRN p.Ala505= (c.1515C>T) in the general population?

GRN p.Ala505= (c.1515C>T) is rare (popmax 0.131%, afr) (gnomAD).

GRN p.Ala505=

Q: What condition is associated with GRN p.Ala505= (c.1515C>T)?

GRN p.Ala505= (c.1515C>T) is associated with Inborn genetic diseases, GRN-related frontotemporal lobar degeneration with Tdp43 inclusions, neuronal ceroid lipofuscinosis 11 (ClinVar).

c.1515C>T · rs147495221 · VCV1573475

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.131%, 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 -7.9	GERP -3
Overall
CADD	0.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% African / African-American · 98/75,080 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.0107% 173/1,614,142 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	766
Admixed American	0.0283%	3,531
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.00364%	27,442

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.Ala505=
Coding: c.1515C>T
MANE Select: NM_002087
dbSNP: rs147495221
Type: single nucleotide variant
Location: chr17:44352442 (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.Ala505Gly 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-ala505 (accessed [today's date]).

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