SDHAF2 p.Arg166=
c.498T>C · rs776140713 · VCV1744591
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, 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 | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.64 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -3.9 |
| Overall | ||
| CADD | 2.518 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,180,034 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,216 alleles · very rare
exomes 3/1,461,880 · genomes 0/152,336 · 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
- SDHAF2
- Protein
- p.Arg166=
- Coding
- c.498T>C
- MANE Select
- NM_017841
- dbSNP
- rs776140713
- Type
- single nucleotide variant
- Location
- chr11:61446068 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.06 · 2 PDB
Similar variants
- SDHAF2 p.Arg166Cys Uncertain significance ★★ ⚠ same residue
- SDHAF2 p.Arg166Leu Uncertain significance ★★ ⚠ same residue
- SDHAF2 p.Arg166His Conflicting classifications of pathogenicity ★ ⚠ same residue
- SDHAF2 c.260+1G>A Likely pathogenic ★★ same condition
- SDHAF2 c.261-2A>G Likely pathogenic ★★ same condition
- SDHAF2 c.261-2A>T Likely pathogenic ★★ same condition
- SDHAF2 c.37-1G>C Pathogenic/Likely pathogenic ★★ same condition
- SDHAF2 c.37-2A>G Pathogenic/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/sdhaf2-p-arg166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown