HTR3A p.Ser447=
c.1341C>T · rs35944954 · VCV781047
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.75%, afr)
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 -12 | GERP -3.9 |
| Overall | ||
| CADD | 2.475 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.75%
African / African-American · 2,062/75,040 alleles
Filtering AF
2.65%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.61%
Overall
0.153%
2,463/1,614,116 alleles · low-frequency
exomes 1,306/1,461,784 · genomes 1,157/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.75% | 36 |
| Remaining individualsnot grpmax-eligible | 0.195% | 512 |
| Admixed American | 0.182% | 551 |
| Middle Eastern | 0.132% | 758 |
| European (non-Finnish) | 0.0128% | 7,815 |
| South Asian | 0.0121% | 8,281 |
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
- HTR3A
- Protein
- p.Ser447=
- Coding
- c.1341C>T
- MANE Select
- NM_000869
- dbSNP
- rs35944954
- Type
- single nucleotide variant
- Location
- chr11:113989667 (GRCh38)
- Gene constraint
- LOEUF 1.034 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.28 · 4 PDB
- Residue 447
- the 'ha-stretch; determines single-channel conductance in 5-ht3 receptors' region; an α-helix
Similar variants
- HTR3A p.Arg27Gln Uncertain significance ★★ ⚠ same type
- HTR3A p.Ile261= Benign ★★ same type
- HTR3A p.Ala230Gly Uncertain significance ★ ⚠ same type
- HTR3A p.Ala299Val Uncertain significance ★ ⚠ same type
- HTR3A p.Ala352Thr Uncertain significance ★ ⚠ same type
- HTR3A p.Ala368Pro Uncertain significance ★ ⚠ same type
- HTR3A p.Ala478Thr Uncertain significance ★ ⚠ same type
- HTR3A p.Ala69Asp 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/htr3a-p-ser447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown