MFF p.Pro54=
c.162G>A · VCV3714795
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.11 | GERP -0.011, phastCons 0.11 |
| Overall | ||
| CADD | 12.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,898 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00266%
43/1,613,924 alleles · ultra-rare
exomes 41/1,461,734 · genomes 2/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,414 |
| Admixed American | 0.00833% | 12,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| European (non-Finnish) | 0.00229% | 43,700 |
| African / African-American | 0.00133% | 74,914 |
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.Pro54=
- Coding
- c.162G>A
- MANE Select
- NM_001277062
- Type
- single nucleotide variant
- Location
- chr2:227330827 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74
Similar variants
- MFF p.Pro54fs Likely pathogenic same residue
- 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
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-pro54 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown