Is HTR2C p.Ser10= (c.30A>C) pathogenic?

HTR2C p.Ser10= (c.30A>C) is classified Likely benign in HTR2C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.000244%, nfe); Associated with HTR2C-related disorder.

What condition is associated with HTR2C p.Ser10= (c.30A>C)?

HTR2C p.Ser10= (c.30A>C) is associated with HTR2C-related disorder (ClinVar).

How common is HTR2C p.Ser10= (c.30A>C) in the general population?

HTR2C p.Ser10= (c.30A>C) is very rare (popmax 0.000244%, nfe) (gnomAD).

HTR2C p.Ser10=

c.30A>C · VCV3348718

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000244%, 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 -5.6	GERP -4
Overall
CADD	0.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000244% European (non-Finnish) · 2/820,836 alleles

Filtering AF 4.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000183% 2/1,094,640 alleles · very rare exomes 2/980,912 · genomes 0/113,728 · 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.Ser10=
Coding: c.30A>C
MANE Select: NM_000868
Type: single nucleotide variant
Location: chrX:114726966 (GRCh38)
Structure: AlphaFold pLDDT 73.71 · 8 PDB

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-ser10 (accessed [today's date]).

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