GRN p.Ser68=
c.204T>C · rs775060160 · VCV3024992
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -1.2 | GERP -2.4 |
| Overall | ||
| CADD | 3.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,952 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00062%
10/1,614,044 alleles · very rare
exomes 7/1,461,786 · genomes 3/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,990 |
| European (non-Finnish) | 0.000424% | 236,005 |
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.Ser68=
- Coding
- c.204T>C
- MANE Select
- NM_002087
- dbSNP
- rs775060160
- Type
- single nucleotide variant
- Location
- chr17:44349491 (GRCh38)
- Gene constraint
- LOEUF 0.59 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 76.74 · 8 PDB
Similar variants
- GRN p.Ser68Pro Uncertain significance ★★ ⚠ same residue
- GRN c.1414-1G>T Pathogenic ★★ same type
- GRN c.1414-2A>G Pathogenic ★★ same type
- GRN c.264+1G>A Likely pathogenic ★★ same type
- GRN c.349+1G>C Pathogenic ★★ same type
- GRN c.599-1G>A Pathogenic/Likely pathogenic ★★ same type
- GRN c.709-1G>A Pathogenic ★★ same type
- GRN c.709-2A>G Pathogenic ★★ same type
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-ser68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown