MFF p.Thr233=
c.699G>A · rs142676012 · VCV512924
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0935%, afr)
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 -2.5 | GERP -4.6 |
| Overall | ||
| CADD | 4.483 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0935%
African / African-American · 70/74,866 alleles
Filtering AF
0.0758%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0694%
Overall
0.00478%
77/1,611,866 alleles · ultra-rare
exomes 35/1,459,710 · genomes 42/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0935% | 1,070 |
| Admixed American | 0.00334% | 29,984 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,402 |
| South Asian | 0.0011% | 90,998 |
| European (non-Finnish) | 0.000255% | 392,759 |
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.Thr233=
- Coding
- c.699G>A
- MANE Select
- NM_001277062
- dbSNP
- rs142676012
- Type
- single nucleotide variant
- Location
- chr2:227355716 (GRCh38)
- Gene constraint
- LOEUF 0.623 · pLI 0.65 (gnomAD)
- Structure
- AlphaFold pLDDT 64.74
Similar variants
- MFF p.Thr233Ala Uncertain significance ★ ⚠ 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-thr233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown