MFF p.Leu85=
c.253C>T · rs781439237 · VCV509660
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 0.61, phastCons 1 |
| Overall | ||
| CADD | 12.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,974 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00328%
53/1,613,644 alleles · ultra-rare
exomes 50/1,461,428 · genomes 3/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,613 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,495 |
| European (non-Finnish) | 0.00288% | 34,698 |
| South Asian | 0.0011% | 91,030 |
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
- MFF
- Protein
- p.Leu85=
- Coding
- c.253C>T
- MANE Select
- NM_001277062
- dbSNP
- rs781439237
- Type
- single nucleotide variant
- Location
- chr2:227332490 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74
Similar variants
- MFF p.Arg128Trp Uncertain significance ★★ ⚠ same type
- MFF p.Arg136Cys Uncertain significance ★★ ⚠ same type
- MFF p.Arg136His Uncertain significance ★★ ⚠ same type
- MFF p.Arg199His Uncertain significance ★★ ⚠ same type
- MFF p.Arg6Gln Uncertain significance ★★ ⚠ same type
- MFF p.Arg92His Uncertain significance ★★ ⚠ same type
- MFF p.Asp75Asn Uncertain significance ★★ ⚠ same type
- MFF p.Gln52His 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/mff-p-leu85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown