Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.37%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.24 | GERP -2.3, phastCons 0.001 |
| Overall | ||
| CADD | 5.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.37%
African / African-American · 4,026/75,012 alleles
Filtering AF
5.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.17%
Overall
0.286%
4,613/1,614,140 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.37% | 19 |
| Admixed American | 0.36% | 278 |
| Remaining individualsnot grpmax-eligible | 0.315% | 317 |
| Middle Eastern | 0.0825% | 1,212 |
| European (non-Finnish) | 0.0136% | 7,375 |
| South Asian | 0.00988% | 10,120 |
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
- DIRAS2
- Protein
- p.Ala138=
- Coding
- c.414C>T
- MANE Select
- NM_017594
- dbSNP
- rs2231776
- Type
- single nucleotide variant
- Location
- chr9:90613414 (GRCh38)
- Gene constraint
- LOEUF 0.782 · pLI 0.46 (gnomAD)
- Structure
- AlphaFold pLDDT 88.69 · 2 PDB
- Residue 138
- an α-helix
Similar variants
- DIRAS2 p.Asp51= Benign ★★ same type
- DIRAS2 p.Ala146Thr Uncertain significance ★ ⚠ same type
- DIRAS2 p.Arg73Gln Uncertain significance ★ ⚠ same type
- DIRAS2 p.Gln177Arg Uncertain significance ★ ⚠ same type
- DIRAS2 p.Glu190Asp Uncertain significance ★ ⚠ same type
- DIRAS2 p.Ile88Val Uncertain significance ★ ⚠ same type
- DIRAS2 p.Pro127Leu Uncertain significance ★ ⚠ same type
- DIRAS2 p.Ser53Asn 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/diras2-p-ala138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown