MFF p.Ala209=
c.627C>T · rs747421782 · VCV2701269
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 2.3, phastCons 1 |
| Overall | ||
| CADD | 15.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,080 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00192%
31/1,613,654 alleles · ultra-rare
exomes 28/1,461,536 · genomes 3/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,080 |
| East Asian | 0.00891% | 11,222 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,616 |
| Admixed American | 0.00334% | 29,981 |
| Finnishnot grpmax-eligible | 0.00156% | 63,984 |
| European (non-Finnish) | 0.00144% | 69,400 |
| African / African-American | 0.00134% | 74,892 |
| South Asian | 0.0011% | 91,080 |
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.Ala209=
- Coding
- c.627C>T
- MANE Select
- NM_001277062
- dbSNP
- rs747421782
- Type
- single nucleotide variant
- Location
- chr2:227352541 (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-ala209 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown