TKFC p.Pro131=
c.393G>A · VCV3910880
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -10 | GERP -3.8 |
| Overall | ||
| CADD | 0.549 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00297%
48/1,613,700 alleles · ultra-rare
exomes 42/1,461,466 · genomes 6/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| European (non-Finnish) | 0.00364% | 27,443 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| South Asian | 0.0022% | 45,545 |
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.Pro131=
- Coding
- c.393G>A
- MANE Select
- NM_015533
- Type
- single nucleotide variant
- Location
- chr11:61339342 (GRCh38)
- Gene constraint
- LOEUF 0.968 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.40
- Residue 131
- 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-pro131 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown