Is GNAL p.Val249= (c.747C>G) pathogenic?

GNAL p.Val249= (c.747C>G) is classified Likely benign in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). Absent from gnomAD v4.1; Associated with dystonic disorder.

What condition is associated with GNAL p.Val249= (c.747C>G)?

GNAL p.Val249= (c.747C>G) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Val249= (c.747C>G) in the general population?

GNAL p.Val249= (c.747C>G) is absent from gnomAD v4.1 (gnomAD).

GNAL p.Val249=

c.747C>G · rs2510466727 · VCV1952636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP 0.85, phastCons 1
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

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: GNAL
Protein: p.Val249=
Coding: c.747C>G
MANE Select: NM_182978
dbSNP: rs2510466727
Type: single nucleotide variant
Location: chr18:11862419 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 249: the g-alpha domain

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

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNAL p.Val249Ile Uncertain significance ★ ⚠ same residue
GNAL p.Val249Leu Uncertain significance ★ ⚠ same residue
GNAL p.Arg322Ter Pathogenic ★★ same condition
GNAL p.Arg400Lys Uncertain significance ★★ ⚠ same condition
GNAL p.Asp220Asn Uncertain significance ★★ ⚠ same condition
GNAL p.Gly417Ser Uncertain significance ★★ ⚠ same condition
GNAL p.Ile351Thr Uncertain significance ★★ ⚠ same condition
GNAL p.Thr414Met 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/gnal-p-val249 (accessed [today's date]).

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