TKFC p.Ala99=
c.297C>T · rs75924231 · VCV1335071
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.769%, 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 -4.8 | GERP -3.8 |
| Overall | ||
| CADD | 4.001 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.769%
African / African-American · 577/75,074 alleles
Filtering AF
0.717%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.696%
Overall
0.0463%
747/1,613,576 alleles · rare
exomes 400/1,461,212 · genomes 347/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.769% | 130 |
| Remaining individualsnot grpmax-eligible | 0.0688% | 1,453 |
| Middle Eastern | 0.0661% | 1,512 |
| Admixed American | 0.0417% | 2,400 |
| European (non-Finnish) | 0.00805% | 12,420 |
| East Asian | 0.00223% | 44,878 |
| South Asian | 0.0022% | 45,526 |
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
- TKFC
- Protein
- p.Ala99=
- Coding
- c.297C>T
- MANE Select
- NM_015533
- dbSNP
- rs75924231
- Type
- single nucleotide variant
- Location
- chr11:61339169 (GRCh38)
- Gene constraint
- LOEUF 0.968 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.40
- Residue 99
- the dhak domain
Similar variants
- TKFC p.Arg543Ile Likely pathogenic ★★ same type
- TKFC p.Arg228Gln Uncertain significance ★★ ⚠ same type
- TKFC p.Asp403Asn Uncertain significance ★★ ⚠ same type
- TKFC p.Gln257Pro Uncertain significance ★★ ⚠ same type
- TKFC c.194-13C>T Benign ★★ same type
- TKFC c.775+39A>C Benign ★★ same type
- TKFC p.Ala185Thr Benign ★★ same type
- TKFC p.Thr157= Benign ★★ 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/tkfc-p-ala99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown