LHB p.Pro27=
c.81A>T · rs374140759 · VCV2084609
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | |
| Overall | ||
| CADD | 0.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
African / African-American · 25/74,744 alleles
Filtering AF
0.0232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00223%
36/1,612,042 alleles · ultra-rare
exomes 20/1,460,080 · genomes 16/151,962 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0334% | 2,990 |
| Admixed American | 0.0167% | 5,998 |
| European (non-Finnish) | 8.48e-05% | 1,179,816 |
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
- LHB
- Protein
- p.Pro27=
- Coding
- c.81A>T
- MANE Select
- NM_000894
- dbSNP
- rs374140759
- Type
- single nucleotide variant
- Location
- chr19:49016649 (GRCh38)
- Gene constraint
- LOEUF 1.603 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.33
Similar variants
- LHB p.Pro27Leu Uncertain significance ★ ⚠ same residue
- LHB p.His30Arg Uncertain significance ★★ ⚠ same type
- LHB p.Pro59Ala Uncertain significance ★★ ⚠ same type
- LHB p.Pro93Arg Uncertain significance ★★ ⚠ same type
- LHB p.Val96Met Uncertain significance ★★ ⚠ same type
- LHB c.15+72C>A Likely benign ★★ same type
- LHB c.15+9A>G Benign ★★ same type
- LHB c.16-104G>C Likely 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/lhb-p-pro27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown