HTR2A p.Leu229=
c.687C>T · rs141413930 · VCV723564
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.235%, 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 -6.8 | GERP -3.8 |
| Overall | ||
| CADD | 0.126 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.235%
European (non-Finnish) · 2,776/1,179,934 alleles
Filtering AF
0.228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.225%
Overall
0.187%
3,018/1,614,012 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.235% | 425 |
| Finnishnot grpmax-eligible | 0.178% | 562 |
| Remaining individualsnot grpmax-eligible | 0.125% | 801 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0541% | 1,850 |
| African / African-American | 0.0413% | 2,420 |
| Admixed American | 0.00333% | 29,999 |
| South Asian | 0.0011% | 91,078 |
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
- HTR2A
- Protein
- p.Leu229=
- Coding
- c.687C>T
- MANE Select
- NM_000621
- dbSNP
- rs141413930
- Type
- single nucleotide variant
- Location
- chr13:46835566 (GRCh38)
- Gene constraint
- LOEUF 0.632 · pLI 0.36 (gnomAD)
- Structure
- AlphaFold pLDDT 74.03 · 47 PDB
- Residue 229
- a functional site (hydrophobic barrier that decreases the speed of ligand binding and dissociation)
Similar variants
- HTR2A p.Ala447Val Likely benign ★★ same type
- HTR2A p.Ser17= Benign ★★ same type
- HTR2A p.Ser219= Likely benign ★★ same type
- HTR2A p.Ser34= Likely benign ★★ same type
- HTR2A p.Ser62= Likely benign ★★ same type
- HTR2A c.412+1G>C Uncertain significance ★ same type
- HTR2A p.Ala230Thr Uncertain significance ★ ⚠ same type
- HTR2A p.Ala447Thr 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/htr2a-p-leu229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown