TKFC p.Pro461=
c.1383C>G · rs1443530048 · VCV2641825
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00119%, 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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -5 |
| Overall | ||
| CADD | 0.687 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
European (non-Finnish) · 14/1,180,036 alleles
Filtering AF
0.000688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.000868%
14/1,613,280 alleles · very rare
exomes 12/1,461,052 · genomes 2/152,228 · joint denominator
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.Pro461=
- Coding
- c.1383C>G
- MANE Select
- NM_015533
- dbSNP
- rs1443530048
- Type
- single nucleotide variant
- Location
- chr11:61345497 (GRCh38)
- Gene constraint
- LOEUF 0.968 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.40
- Residue 461
- the dhal 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-pro461 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown