SDHA p.Leu7=
c.21G>A · rs2126522394 · VCV3223739
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.98e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
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 0.22, phastCons 0.98 |
| Overall | ||
| CADD | 7.205 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.98e-05%
European (non-Finnish) · 1/1,113,198 alleles
Overall
6.86e-05%
1/1,456,778 alleles · very rare
exomes 1/1,304,494 · genomes 0/152,284 · 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
- SDHA
- Protein
- p.Leu7=
- Coding
- c.21G>A
- MANE Select
- NM_004168
- dbSNP
- rs2126522394
- Type
- single nucleotide variant
- Location
- chr5:218376 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.06 · 5 PDB
Similar variants
- SDHA p.Leu7Pro Uncertain significance ★★ ⚠ same residue
- SDHA p.Leu7Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- SDHA c.1064+1G>T Likely pathogenic ★★ same condition
- SDHA c.1064+2T>A Likely pathogenic ★★ same condition
- SDHA c.1261-1G>A Likely pathogenic ★★ same condition
- SDHA c.1261-2A>G Likely pathogenic ★★ same condition
- SDHA c.151-1G>C Likely pathogenic ★★ same condition
- SDHA c.151-2A>G Likely pathogenic ★★ 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/sdha-p-leu7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown