TFR2 p.Val454=
c.1362G>A · rs2131314908 · VCV1563321
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
1
hereditary hemochromatosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.46 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.24 | gain · loss 0.16 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP -7.5, phastCons 0.24 |
| Overall | ||
| CADD | 15.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,090 alleles
Overall
0.000124%
2/1,614,076 alleles · very rare
exomes 2/1,461,744 · genomes 0/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,090 |
| European (non-Finnish) | 8.48e-05% | 1,179,940 |
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.Val454=
- Coding
- c.1362G>A
- MANE Select
- NM_003227
- dbSNP
- rs2131314908
- Type
- single nucleotide variant
- Location
- chr7:100629281 (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 p.Val454Ala 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
- TFR2 c.34-2A>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-val454 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown