SGPL1 p.Ser367=
c.1101T>C · rs972818538 · VCV1557888
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
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 -2.2 | GERP -2.4 |
| Overall | ||
| CADD | 6.968 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,010 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00578%
Overall
0.000681%
11/1,614,120 alleles · ultra-rare
exomes 8/1,461,878 · genomes 3/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,668 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| European (non-Finnish) | 8.47e-05% | 1,180,038 |
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
- SGPL1
- Protein
- p.Ser367=
- Coding
- c.1101T>C
- MANE Select
- NM_003901
- dbSNP
- rs972818538
- Type
- single nucleotide variant
- Location
- chr10:70873392 (GRCh38)
- Gene constraint
- LOEUF 0.71 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07 · 2 PDB
- Residue 367
- a UniProt-annotated variant site (found in patients with atypical form of axonal peripheral neuropathy, characterized by acute or subacute onset and episodes of recurrent mononeuropathy; likely pathogenic); a β-strand
Similar variants
- SGPL1 p.Arg222Gln Pathogenic ★★ same type
- SGPL1 p.Arg495Ter Pathogenic ★★ same type
- SGPL1 p.Arg505Ter Pathogenic ★★ same type
- SGPL1 p.Tyr331Ter Pathogenic ★★ same type
- SGPL1 p.Tyr416Cys Likely pathogenic ★★ same type
- SGPL1 p.Ala316Thr Uncertain significance ★★ ⚠ same type
- SGPL1 p.Ala492Ser Uncertain significance ★★ ⚠ same type
- SGPL1 p.Arg278Gly Uncertain significance ★★ ⚠ 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/sgpl1-p-ser367 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown