FHIT p.Phe23=
c.69C>T · rs746373823 · VCV741725
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0915%, 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 -0.85 | GERP -4.4 |
| Overall | ||
| CADD | 8.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0915%
East Asian · 41/44,826 alleles
Filtering AF
0.0693%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0615%
Overall
0.00484%
78/1,612,522 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0915% | 1,093 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,805 |
| Admixed American | 0.01% | 9,977 |
| European (non-Finnish) | 0.00187% | 53,606 |
| Finnishnot grpmax-eligible | 0.00157% | 63,860 |
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
- FHIT
- Protein
- p.Phe23=
- Coding
- c.69C>T
- MANE Select
- NM_002012
- dbSNP
- rs746373823
- Type
- single nucleotide variant
- Location
- chr3:60536894 (GRCh38)
- Gene constraint
- LOEUF 1.57 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.15 · 9 PDB
- Residue 23
- the hit domain; a β-strand
Similar variants
- FHIT p.Ala127Asp Uncertain significance ★ ⚠ same type
- FHIT p.Ala141Ser Uncertain significance ★ ⚠ same type
- FHIT p.Ala24Pro Uncertain significance ★ ⚠ same type
- FHIT p.Arg46Cys Uncertain significance ★ ⚠ same type
- FHIT p.Arg46His Uncertain significance ★ ⚠ same type
- FHIT p.Arg51His Uncertain significance ★ ⚠ same type
- FHIT p.Asn110Ser Uncertain significance ★ ⚠ same type
- FHIT p.Cys39Tyr Uncertain significance ★ ⚠ 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/fhit-p-phe23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown