Is HTR2C p.Val78= (c.234A>T) pathogenic?

HTR2C p.Val78= (c.234A>T) is classified Likely benign in HTR2C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-21). Ultra-rare (popmax 0.0196%, amr); Associated with HTR2C-related disorder.

What condition is associated with HTR2C p.Val78= (c.234A>T)?

HTR2C p.Val78= (c.234A>T) is associated with HTR2C-related disorder (ClinVar).

How common is HTR2C p.Val78= (c.234A>T) in the general population?

HTR2C p.Val78= (c.234A>T) is ultra-rare (popmax 0.0196%, amr) (gnomAD).

HTR2C p.Val78=

c.234A>T · VCV3351340

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, amr)

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 1	GERP -6.8, phastCons 0.99
Overall
CADD	2.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0196% Admixed American · 9/45,980 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00753%

Overall 0.000748% 9/1,203,631 alleles · ultra-rare exomes 9/1,090,345 · genomes 0/113,286 · 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.Val78=
Coding: c.234A>T
MANE Select: NM_000868
Type: single nucleotide variant
Location: chrX:114731492 (GRCh38)
Structure: AlphaFold pLDDT 73.71 · 8 PDB
Residue 78: 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-val78 (accessed [today's date]).

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