TFR2 p.Arg752=
c.2256C>G · rs963087261 · VCV2806944
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00051%, nfe)
Conditions
1
hereditary hemochromatosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.012, phastCons 0.97 |
| Overall | ||
| CADD | 2.178 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00051%
European (non-Finnish) · 6/1,176,752 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000121%
Overall
0.000374%
6/1,606,154 alleles · very rare
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.Arg752=
- Coding
- c.2256C>G
- MANE Select
- NM_003227
- dbSNP
- rs963087261
- Type
- single nucleotide variant
- Location
- chr7:100621007 (GRCh38)
- Gene constraint
- LOEUF 0.907 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.98
- Residue 752
- a UniProt-annotated variant site (in)
Similar variants
- TFR2 p.Arg752His Benign/Likely benign ★★ same residue
- TFR2 p.Arg752Cys Uncertain significance ★ ⚠ same residue
- 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
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-arg752 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown