SAMD9 p.Glu666=
c.1998G>A · rs768512497 · VCV1336917
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Conditions
1
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 0.69 | phastCons 0.99 |
| Overall | ||
| CADD | 1.905 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,018 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00062%
10/1,613,930 alleles · ultra-rare
exomes 10/1,461,674 · genomes 0/152,256 · joint denominator
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
- SAMD9
- Protein
- p.Glu666=
- Coding
- c.1998G>A
- MANE Select
- NM_017654
- dbSNP
- rs768512497
- Type
- single nucleotide variant
- Location
- chr7:93104100 (GRCh38)
- Gene constraint
- LOEUF 1.773 · pLI 0.03 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 83.79 · 10 PDB
Similar variants
- SAMD9 p.Glu666Lys Uncertain significance ★ ⚠ same residue
- SAMD9 p.Ala1057Val Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala1069Thr Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala1082Gly Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala1102Asp Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala1195Asp Uncertain significance ★★ ⚠ same condition
- SAMD9 p.Ala123Ser Uncertain significance ★★ ⚠ 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/samd9-p-glu666 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown