ST14 p.Ser539=
c.1617G>A · VCV4753637
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.292%, 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 -4.1 | GERP -4.4 |
| Overall | ||
| CADD | 1.054 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.292%
South Asian · 266/91,084 alleles
Filtering AF
0.263%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.252%
Overall
0.0224%
362/1,614,078 alleles · rare
exomes 341/1,461,776 · genomes 21/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.292% | 342 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0338% | 2,960 |
| Middle Eastern | 0.033% | 3,029 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,465 |
| African / African-American | 0.00933% | 10,721 |
| European (non-Finnish) | 0.00534% | 18,731 |
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
- ST14
- Protein
- p.Ser539=
- Coding
- c.1617G>A
- MANE Select
- NM_021978
- Type
- single nucleotide variant
- Location
- chr11:130198554 (GRCh38)
- Gene constraint
- LOEUF 0.589 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.23 · 25 PDB
- Residue 539
- the ldl-receptor class a 3 domain
Similar variants
- ST14 p.Ala557Thr Uncertain significance ★★ ⚠ same type
- ST14 p.Arg227Gly Uncertain significance ★★ ⚠ same type
- ST14 p.Gly272Ser Uncertain significance ★★ ⚠ same type
- ST14 p.Gly642Ser Uncertain significance ★★ ⚠ same type
- ST14 p.Lys743Asn Uncertain significance ★★ ⚠ same type
- ST14 p.Pro526Leu Uncertain significance ★★ ⚠ same type
- ST14 p.Ser449Phe Uncertain significance ★★ ⚠ same type
- ST14 p.Thr419Ala 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/st14-p-ser539 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown