FH p.Ala23=
c.69T>C · VCV4642269
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.72e-05%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.006 | GERP -2.4 |
| Overall | ||
| CADD | 6.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.72e-05%
European (non-Finnish) · 1/1,146,480 alleles
Overall
7.16e-05%
1/1,395,696 alleles · very rare
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.Ala23=
- Coding
- c.69T>C
- MANE Select
- NM_000143
- Type
- single nucleotide variant
- Location
- chr1:241519654 (GRCh38)
- Gene constraint
- LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.92 · 8 PDB
Similar variants
- FH p.Ala23Thr Uncertain significance ★★ ⚠ same residue
- FH p.Ala23Val Uncertain significance ★★ ⚠ same residue
- FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ same condition
- FH c.1236+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FH c.1236+1G>C Pathogenic ★★ same condition
- FH c.1236+2T>G Pathogenic ★★ same condition
- FH c.1237-1G>T Likely pathogenic ★★ same condition
- FH c.1390+1G>T 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/fh-p-ala23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown