Is GNAL p.Asp258= (c.774C>T) pathogenic?

GNAL p.Asp258= (c.774C>T) is classified Likely benign in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). Absent from gnomAD v4.1; Associated with dystonic disorder.

What condition is associated with GNAL p.Asp258= (c.774C>T)?

GNAL p.Asp258= (c.774C>T) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Asp258= (c.774C>T) in the general population?

GNAL p.Asp258= (c.774C>T) is absent from gnomAD v4.1 (gnomAD).

GNAL p.Asp258=

c.774C>T · rs2510466772 · VCV2904548

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.99	GERP 0.85, phastCons 1
Overall
CADD	10.61	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.Asp258=
Coding: c.774C>T
MANE Select: NM_182978
dbSNP: rs2510466772
Type: single nucleotide variant
Location: chr18:11862446 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 258: the g-alpha domain; an α-helix

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.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
GNAL c.1163-7T>G Benign ★★ same condition
GNAL c.449+19C>A Benign ★★ 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-asp258 (accessed [today's date]).

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