Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 54.6%, eas) — too common for a highly-penetrant pathogenic allele
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 -1.9 | GERP -4.2 |
| Overall | ||
| CADD | 5.941 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
54.6%
East Asian · 24,524/44,888 alleles
Filtering AF
54.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 53.8%
Overall
40.7%
657,018/1,613,746 alleles · common
exomes 595,959/1,461,692 · genomes 61,059/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 54.6% | 2 |
| Middle Eastern | 52.3% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 50.1% | 2 |
| Remaining individualsnot grpmax-eligible | 42.8% | 2 |
| South Asian | 41.9% | 2 |
| European (non-Finnish) | 40.6% | 2 |
| African / African-American | 37.8% | 3 |
| Admixed American | 35% | 3 |
| Finnishnot grpmax-eligible | 32.5% | 3 |
| Amishnot grpmax-eligible | 22.1% | 5 |
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.Ser34=
- Coding
- c.102C>T
- MANE Select
- NM_000621
- dbSNP
- rs6313
- Type
- single nucleotide variant
- Location
- chr13:46895805 (GRCh38)
- Gene constraint
- LOEUF 0.632 · pLI 0.36 (gnomAD)
- Structure
- AlphaFold pLDDT 74.03 · 47 PDB
Similar variants
- HTR2A p.Ala447Val Likely benign ★★ same type
- HTR2A p.Leu229= Benign/Likely benign ★★ same type
- HTR2A p.Ser17= Benign ★★ same type
- HTR2A p.Ser219= 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-ser34 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown