GRN p.Phe507=
c.1521C>T · rs140070738 · VCV888744
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0028%, nfe)
Conditions
2
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions
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 0.62 | GERP 0.24, phastCons 0.007 |
| Overall | ||
| CADD | 5.125 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0028%
European (non-Finnish) · 33/1,180,002 alleles
Filtering AF
0.00199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00175%
Overall
0.00211%
34/1,614,014 alleles · very rare
exomes 31/1,461,778 · genomes 3/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0028% | 35,758 |
| Admixed American | 0.00167% | 60,014 |
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.Phe507=
- Coding
- c.1521C>T
- MANE Select
- NM_002087
- dbSNP
- rs140070738
- Type
- single nucleotide variant
- Location
- chr17:44352448 (GRCh38)
- Gene constraint
- LOEUF 0.59 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 8 PDB
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-phe507 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown