TFAM p.Ser61=
c.183T>C · rs78325627 · VCV669577
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.89%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss, 24 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.018 | GERP -1.9, phastCons 0.55 |
| Overall | ||
| CADD | 7.035 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.89%
Middle Eastern · 172/5,944 alleles
Filtering AF
2.54%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.41%
Overall
1.86%
29,979/1,613,840 alleles · low-frequency
exomes 27,654/1,461,518 · genomes 2,325/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.89% | 35 |
| Finnishnot grpmax-eligible | 2.49% | 40 |
| European (non-Finnish) | 2.07% | 48 |
| Ashkenazi Jewishnot grpmax-eligible | 1.86% | 54 |
| Remaining individualsnot grpmax-eligible | 1.83% | 55 |
| Admixed American | 1.54% | 65 |
| Amishnot grpmax-eligible | 1.54% | 65 |
| South Asian | 1.05% | 95 |
| African / African-American | 0.304% | 329 |
| East Asian | 0.00446% | 22,434 |
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.Ser61=
- Coding
- c.183T>C
- MANE Select
- NM_003201
- dbSNP
- rs78325627
- Type
- single nucleotide variant
- Location
- chr10:58386301 (GRCh38)
- Gene constraint
- LOEUF 0.742 · pLI 0.09 (gnomAD)
- Structure
- AlphaFold pLDDT 86.06 · 16 PDB
- Residue 61
- a DNA-binding region; an α-helix; a modified residue (phosphoserine; by pka)
Similar variants
- 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
- TFAM p.Met143Ile 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-ser61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown