SDHA c.1663+20T>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
pheochromocytoma/paraganglioma syndrome 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +20 | near-intronic (+20 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -1.9 |
| Non-coding constraint | Z 2.75 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 0.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,008 alleles
Overall
0.000125%
2/1,595,816 alleles · very rare
exomes 2/1,443,472 · genomes 0/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,008 |
| European (non-Finnish) | 8.58e-05% | 1,165,088 |
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
- Coding
- c.1663+20T>C
- MANE Select
- NM_004168
- dbSNP
- rs1226482893
- Type
- single nucleotide variant
- Location
- chr5:251123 (GRCh38)
- Gene constraint
- LOEUF 0.786 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.06 · 5 PDB
Similar variants
- SDHA c.1064+1G>A Likely pathogenic ★★ same condition
- SDHA c.1064+1G>T Likely pathogenic ★★ same condition
- SDHA c.1064+2T>A Likely pathogenic ★★ same condition
- SDHA c.1065-2A>G Likely pathogenic ★★ same condition
- SDHA c.1260+1G>T Likely pathogenic ★★ same condition
- SDHA c.1260+2T>A Likely pathogenic ★★ same condition
- SDHA c.1261-1G>A Likely pathogenic ★★ same condition
- SDHA c.1261-2A>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-c-1663-plus-20t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown