TFR2 p.Arg57=
c.171G>A · rs758440377 · VCV2888826
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00335%, sas)
Conditions
1
hereditary hemochromatosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.32 | GERP 2, phastCons 0.96 |
| Overall | ||
| CADD | 10.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00335%
South Asian · 3/89,526 alleles
Filtering AF
0.00089%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000447%
Overall
0.0005%
8/1,599,352 alleles · very rare
exomes 7/1,447,092 · genomes 1/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00335% | 29,842 |
| European (non-Finnish) | 0.000427% | 234,457 |
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
- TFR2
- Protein
- p.Arg57=
- Coding
- c.171G>A
- MANE Select
- NM_003227
- dbSNP
- rs758440377
- Type
- single nucleotide variant
- Location
- chr7:100641091 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.98
Similar variants
- TFR2 c.1473+1G>A Likely pathogenic ★★ same condition
- TFR2 c.1474-1G>A Likely pathogenic ★★ same condition
- TFR2 c.1606-2A>G Pathogenic ★★ same condition
- TFR2 c.1767+1G>T Likely pathogenic ★★ same condition
- TFR2 c.286+1G>T Likely pathogenic ★★ same condition
- TFR2 c.286+2T>C Likely pathogenic ★★ same condition
- TFR2 c.34-2A>G Likely pathogenic ★★ same condition
- TFR2 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same condition
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/tfr2-p-arg57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown