SDHA c.1663+3G>C
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
4
pheochromocytoma/paraganglioma syndrome 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.53 | donor loss · deltas |
| Pangolin | Δ0.71 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP 0.32, phastCons 1 |
| Non-coding constraint | Z 2.75 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 16.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,000 alleles
Filtering AF
0.000689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00137%
22/1,611,152 alleles · very rare
exomes 17/1,458,940 · genomes 5/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,000 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,138 |
| East Asian | 0.00223% | 44,884 |
| South Asian | 0.0022% | 45,491 |
| African / African-American | 0.00134% | 74,832 |
| European (non-Finnish) | 0.00119% | 84,228 |
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+3G>C
- MANE Select
- NM_004168
- dbSNP
- rs751904543
- Type
- single nucleotide variant
- Location
- chr5:251106 (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-3g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown