Is HTR2C p.Ser334= (c.1002T>G) pathogenic?

HTR2C p.Ser334= (c.1002T>G) is classified Likely benign in HTR2C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-14). Very rare (popmax 0.00112%, nfe); Associated with HTR2C-related disorder.

What condition is associated with HTR2C p.Ser334= (c.1002T>G)?

HTR2C p.Ser334= (c.1002T>G) is associated with HTR2C-related disorder (ClinVar).

How common is HTR2C p.Ser334= (c.1002T>G) in the general population?

HTR2C p.Ser334= (c.1002T>G) is very rare (popmax 0.00112%, nfe) (gnomAD).

HTR2C p.Ser334=

c.1002T>G · rs143723100 · VCV3036821

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Conditions

HTR2C-related disorder

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 -4.6	GERP -12
Overall
CADD	0.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% European (non-Finnish) · 10/894,215 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000827% 10/1,208,713 alleles · very rare exomes 8/1,097,007 · genomes 2/111,706 · joint denominator

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: HTR2C
Protein: p.Ser334=
Coding: c.1002T>G
MANE Select: NM_000868
dbSNP: rs143723100
Type: single nucleotide variant
Location: chrX:114907040 (GRCh38)
Structure: AlphaFold pLDDT 73.71 · 8 PDB
Residue 334: an α-helix

Full HTR2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HTR2C-related disorder

Similar variants

HTR2C p.Val8= Uncertain significance ★ same condition
HTR2C c.349+2T>C Uncertain significance same condition
HTR2C p.Arg288Ter Uncertain significance same condition
HTR2C p.Arg295Cys Uncertain significance ⚠ same condition
HTR2C p.Arg295Gly Uncertain significance ⚠ same condition
HTR2C p.Arg400Ser Uncertain significance ⚠ same condition
HTR2C p.Arg454Met Uncertain significance ⚠ same condition
HTR2C p.Asn166Ser Uncertain significance ⚠ same condition

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/htr2c-p-ser334 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown