TFAM p.Pro178=
c.534G>A · rs371492198 · VCV1320584
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.134%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.019 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.63 | GERP -3.2, phastCons 0.005 |
| Overall | ||
| CADD | 6.272 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.134%
South Asian · 122/90,948 alleles
Filtering AF
0.115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.107%
Overall
0.0201%
324/1,611,710 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.134% | 745 |
| Middle Eastern | 0.0336% | 2,977 |
| European (non-Finnish) | 0.0154% | 6,477 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,932 |
| Finnishnot grpmax-eligible | 0.011% | 9,059 |
| African / African-American | 0.00267% | 37,437 |
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
- TFAM
- Protein
- p.Pro178=
- Coding
- c.534G>A
- MANE Select
- NM_003201
- dbSNP
- rs371492198
- Type
- single nucleotide variant
- Location
- chr10:58390857 (GRCh38)
- Gene constraint
- LOEUF 0.742 · pLI 0.09 (gnomAD)
- Structure
- AlphaFold pLDDT 86.06 · 16 PDB
- Residue 178
- a UniProt-annotated variant site (in mtdps15); an α-helix; a DNA-binding region
Similar variants
- TFAM p.Pro178Leu Likely pathogenic ★ ⚠ same residue
- TFAM p.Ala47Thr Uncertain significance ★★ ⚠ same type
- TFAM p.Arg159Cys Uncertain significance ★★ ⚠ same type
- TFAM p.Arg233Cys Uncertain significance ★★ ⚠ same type
- TFAM p.Gln100Glu Uncertain significance ★★ ⚠ same type
- TFAM p.Leu4Val Uncertain significance ★★ ⚠ same type
- TFAM p.Lys205Glu Uncertain significance ★★ ⚠ same type
- TFAM p.Lys228Arg 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/tfam-p-pro178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown