SDHA p.Arg623=
c.1869G>A · rs2477476846 · VCV1781626
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
Conditions
2
pheochromocytoma/paraganglioma syndrome 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.331 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP -1.9, phastCons 1 |
| Overall | ||
| CADD | 9.833 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,134 alleles
Overall
6.3e-05%
1/1,586,432 alleles · very rare
exomes 1/1,434,446 · genomes 0/151,986 · 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.Arg623=
- Coding
- c.1869G>A
- MANE Select
- NM_004168
- dbSNP
- rs2477476846
- Type
- single nucleotide variant
- Location
- chr5:254467 (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-p-arg623 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown