TFR2 p.Arg652=
c.1956G>A · rs1170988281 · VCV911963
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0212%, mid)
Conditions
2
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 -0.23 | GERP 0.79, phastCons 0.17 |
| Overall | ||
| CADD | 8.154 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0212%
Middle Eastern · 1/4,706 alleles
Filtering AF
7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000323%
5/1,549,484 alleles · ultra-rare
exomes 4/1,397,260 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0212% | 4,706 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,932 |
| European (non-Finnish) | 0.000262% | 382,288 |
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.Arg652=
- Coding
- c.1956G>A
- MANE Select
- NM_003227
- dbSNP
- rs1170988281
- Type
- single nucleotide variant
- Location
- chr7:100627303 (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.1606-8A>G Likely 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.287-2A>G 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-arg652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown