FOXC2 p.Lys142=
c.426G>A · rs41312258 · VCV707267
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.64%, sas)
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 4.3 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 16.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.64%
South Asian · 1,492/91,080 alleles
Filtering AF
1.57%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.54%
Overall
0.423%
6,823/1,614,176 alleles · low-frequency
exomes 6,380/1,461,856 · genomes 443/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.64% | 61 |
| Middle Eastern | 0.479% | 209 |
| Remaining individualsnot grpmax-eligible | 0.416% | 240 |
| European (non-Finnish) | 0.411% | 243 |
| Admixed American | 0.178% | 561 |
| African / African-American | 0.0746% | 1,340 |
| Finnishnot grpmax-eligible | 0.025% | 4,001 |
| East Asian | 0.0111% | 8,971 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,869 |
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
- FOXC2
- Protein
- p.Lys142=
- Coding
- c.426G>A
- MANE Select
- NM_005251
- dbSNP
- rs41312258
- Type
- single nucleotide variant
- Location
- chr16:86567761 (GRCh38)
- Gene constraint
- LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.45 · 8 PDB
- Residue 142
- a DNA-binding region; a β-strand
Similar variants
- FOXC2 p.Lys142Asn Uncertain significance ★ ⚠ same residue
- FOXC2 p.Arg121Cys Pathogenic/Likely pathogenic ★★ same type
- FOXC2 p.Gln100Ter Pathogenic ★★ same type
- FOXC2 p.Leu124Phe Likely pathogenic ★★ same type
- FOXC2 p.Tyr99Ter Pathogenic/Likely pathogenic ★★ same type
- FOXC2 p.Ala194Ser Uncertain significance ★★ ⚠ same type
- FOXC2 p.Ala326Gly Uncertain significance ★★ ⚠ same type
- FOXC2 p.Gln238Lys 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/foxc2-p-lys142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown