Is GNAL p.Ala41= (c.123T>C) pathogenic?

GNAL p.Ala41= (c.123T>C) is classified Likely benign in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Very rare (popmax 0.00168%, amr); Associated with dystonic disorder.

What condition is associated with GNAL p.Ala41= (c.123T>C)?

GNAL p.Ala41= (c.123T>C) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Ala41= (c.123T>C) in the general population?

GNAL p.Ala41= (c.123T>C) is very rare (popmax 0.00168%, amr) (gnomAD).

GNAL p.Ala41=

c.123T>C · VCV4708065

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

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 0.26	GERP -4.1, phastCons 0.96
Overall
CADD	15.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,692 alleles

Overall 6.21e-05% 1/1,611,008 alleles · very rare exomes 1/1,458,780 · genomes 0/152,228 · 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: GNAL
Protein: p.Ala41=
Coding: c.123T>C
MANE Select: NM_182978 · reported on NM_001369387
Type: single nucleotide variant
Location: chr18:11752556 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 41: 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.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-ala41 (accessed [today's date]).

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