FH p.Val73=
c.219G>A · rs1213056420 · VCV1161116
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
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 -0.2, phastCons 1 |
| Overall | ||
| CADD | 10.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,884 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000372%
6/1,614,030 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,961 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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
- FH
- Protein
- p.Val73=
- Coding
- c.219G>A
- MANE Select
- NM_000143
- dbSNP
- rs1213056420
- Type
- single nucleotide variant
- Location
- chr1:241517230 (GRCh38)
- Gene constraint
- LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.92 · 8 PDB
- Residue 73
- an α-helix
Similar variants
- FH p.Val73Ala Uncertain significance ★★ same residue
- FH p.Val73Leu Uncertain significance ★★ ⚠ same residue
- FH p.Val73Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- FH c.1108+1G>A Pathogenic ★★ same type
- FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ same type
- FH c.1236+1G>A Pathogenic/Likely pathogenic ★★ same type
- FH c.1236+1G>C Pathogenic ★★ same type
- FH c.1236+2T>G Pathogenic ★★ same type
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/fh-p-val73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown