Is HTR2A p.Val379Ala (c.1136T>C) pathogenic?

HTR2A p.Val379Ala (c.1136T>C) is classified Uncertain significance in HTR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-21). AlphaMissense: likely pathogenic (0.8998); Absent from gnomAD v4.1.

How common is HTR2A p.Val379Ala (c.1136T>C) in the general population?

HTR2A p.Val379Ala (c.1136T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HTR2A p.Val379Ala (c.1136T>C)?

AlphaMissense predicts likely pathogenic (score 0.8998) — an in-silico prediction, not a clinical call.

HTR2A p.Val379Ala

c.1136T>C · VCV3285029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8998	likely pathogenic
REVEL	0.611	indeterminate
SaProt	LLR -12.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 83 bp · p 0.00029 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HTR2A
Protein: p.Val379Ala
Coding: c.1136T>C
MANE Select: NM_000621
Type: single nucleotide variant
Location: chr13:46835117 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 74.03 · 47 PDB
Residue 379: an α-helix

Full HTR2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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.Ser34= 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

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-val379ala (accessed [today's date]).

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