SGMS2 p.Ala86=
c.258A>C · VCV3674161
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00347%, nfe)
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 -9.9 | GERP -5.8 |
| Overall | ||
| CADD | 0.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00347%
European (non-Finnish) · 41/1,179,954 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.0026%
42/1,613,868 alleles · very rare
exomes 41/1,461,712 · genomes 1/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00347% | 28,779 |
| South Asian | 0.0011% | 91,086 |
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
- SGMS2
- Protein
- p.Ala86=
- Coding
- c.258A>C
- MANE Select
- NM_001375905
- Type
- single nucleotide variant
- Location
- chr4:107895811 (GRCh38)
- Gene constraint
- LOEUF 0.624 · pLI 0.19 (gnomAD)
- Structure
- AlphaFold pLDDT 77.54
- Residue 86
- a UniProt-annotated variant site (in cdl; loss of enzymatic activity; does not localize to plasma membrane)
Similar variants
- SGMS2 p.Arg246His Uncertain significance ★★ ⚠ same type
- SGMS2 p.Pro340Leu Uncertain significance ★★ ⚠ same type
- SGMS2 p.Pro57Leu Uncertain significance ★★ ⚠ same type
- SGMS2 p.Leu258Val Uncertain significance ★ ⚠ same type
- SGMS2 p.Lys51Glu Uncertain significance ★ ⚠ same type
- SGMS2 p.Met1Val Uncertain significance ★ same type
- SGMS2 p.Thr215Ser Uncertain significance ★ ⚠ same type
- SGMS2 p.Val200Leu 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/sgms2-p-ala86 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown