Is GNAL p.Arg44= (c.132C>T) pathogenic?

GNAL p.Arg44= (c.132C>T) is classified Benign/Likely benign in GNAL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0828%, mid); Associated with dystonic disorder.

What condition is associated with GNAL p.Arg44= (c.132C>T)?

GNAL p.Arg44= (c.132C>T) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Arg44= (c.132C>T) in the general population?

GNAL p.Arg44= (c.132C>T) is ultra-rare (popmax 0.0828%, mid) (gnomAD).

GNAL p.Arg44=

c.132C>T · rs145400180 · VCV526222

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0828%, mid)

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 0.85	GERP -4, phastCons 1
Overall
CADD	16.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0828% Middle Eastern · 5/6,038 alleles

Filtering AF 0.0616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0563%

Overall 0.0339% 546/1,610,340 alleles · ultra-rare exomes 518/1,458,096 · genomes 28/152,244 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0847%	1,180
Middle Easterngrpmax	0.0828%	1,208
South Asian	0.0761%	1,314
Remaining individualsnot grpmax-eligible	0.0369%	2,710
European (non-Finnish)	0.0347%	2,882
Admixed American	0.0168%	5,961
African / African-American	0.00537%	18,638
East Asian	0.00227%	44,106

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg44=
Coding: c.132C>T
MANE Select: NM_182978 · reported on NM_001369387
dbSNP: rs145400180
Type: single nucleotide variant
Location: chr18:11752565 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 44: the g-alpha domain; the 'g1 motif' region

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-arg44 (accessed [today's date]).

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