TFRC p.Ser199=
c.597G>A · rs200521798 · VCV1559546
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00551%, nfe)
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 |
|---|---|---|
| Pangolin | Δ0.40 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.4 |
| Overall | ||
| CADD | 0.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00551%
European (non-Finnish) · 65/1,179,938 alleles
Filtering AF
0.00443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00403%
Overall
0.00452%
73/1,613,990 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00551% | 18,153 |
| South Asian | 0.00329% | 30,355 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| African / African-American | 0.00267% | 37,515 |
| Admixed American | 0.00167% | 60,002 |
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.Ser199=
- Coding
- c.597G>A
- MANE Select
- NM_001128148
- dbSNP
- rs200521798
- Type
- single nucleotide variant
- Location
- chr3:196071486 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 86.87 · 24 PDB
- Residue 199
- a β-strand
Similar variants
- TFRC p.Ser199Leu Uncertain significance ★★ ⚠ same residue
- 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
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-ser199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown