MTFMT p.Ala280=
c.840G>A · rs753491878 · VCV1556794
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP -3.4, phastCons 0.033 |
| Overall | ||
| CADD | 8.101 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,038 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000868%
14/1,612,270 alleles · very rare
exomes 13/1,460,196 · genomes 1/152,074 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,759 |
| Admixed American | 0.00167% | 59,962 |
| African / African-American | 0.00134% | 74,826 |
| European (non-Finnish) | 0.000678% | 147,386 |
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
- MTFMT
- Protein
- p.Ala280=
- Coding
- c.840G>A
- MANE Select
- NM_139242
- dbSNP
- rs753491878
- Type
- single nucleotide variant
- Location
- chr15:65006165 (GRCh38)
- Gene constraint
- LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.08
Similar variants
- MTFMT p.Ala280Val Uncertain significance ★★ ⚠ same residue
- MTFMT c.722-2A>G Likely pathogenic ★★ same type
- MTFMT p.Arg128Ter Pathogenic/Likely pathogenic ★★ same type
- MTFMT p.Arg332Ter Pathogenic ★★ same type
- MTFMT p.Ser125Leu Pathogenic/Likely pathogenic ★★ same type
- MTFMT p.Ser209Leu Pathogenic ★★ ⚠ same type
- MTFMT p.Trp9Ter Pathogenic ★★ same type
- MTFMT p.Ala213Thr 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/mtfmt-p-ala280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown