TFRC p.Ser419=
c.1257C>T · rs142218775 · VCV1126875
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.152%, afr)
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 2.6 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 11.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.152%
African / African-American · 114/74,994 alleles
Filtering AF
0.129%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.121%
Overall
0.011%
178/1,613,668 alleles · rare
exomes 98/1,461,414 · genomes 80/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.152% | 658 |
| Admixed American | 0.0367% | 2,723 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,124 |
| South Asian | 0.0022% | 45,516 |
| European (non-Finnish) | 0.0017% | 58,994 |
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.Ser419=
- Coding
- c.1257C>T
- MANE Select
- NM_001128148
- dbSNP
- rs142218775
- Type
- single nucleotide variant
- Location
- chr3:196064370 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 24 PDB
- Residue 419
- an α-helix
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-ser419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown