TFRC p.Arg61=
c.183G>A · rs146583130 · VCV1935773
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.41 | donor loss, 1 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -3.4 |
| Overall | ||
| CADD | 3.261 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
African / African-American · 14/74,896 alleles
Filtering AF
0.0112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.000991%
16/1,614,020 alleles · ultra-rare
exomes 8/1,461,894 · genomes 8/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0187% | 5,350 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,245 |
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
- TFRC
- Protein
- p.Arg61=
- Coding
- c.183G>A
- MANE Select
- NM_001128148
- dbSNP
- rs146583130
- Type
- single nucleotide variant
- Location
- chr3:196075214 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 24 PDB
- Residue 61
- the 'mediates interaction with sh3bp4' region
Similar variants
- TFRC c.1678-3C>T Uncertain significance ★★ same type
- TFRC p.Ala166Val Uncertain significance ★★ ⚠ same type
- TFRC p.Ala196Thr Uncertain significance ★★ ⚠ same type
- TFRC p.Ala293Thr Uncertain significance ★★ ⚠ same type
- TFRC p.Ala540Val Uncertain significance ★★ ⚠ same type
- TFRC p.Ala72Ser Uncertain significance ★★ ⚠ same type
- TFRC p.Arg155His Uncertain significance ★★ ⚠ same type
- TFRC p.Arg155Pro 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/tfrc-p-arg61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown