Is GNAL p.Pro425= (c.1275G>A) pathogenic?

GNAL p.Pro425= (c.1275G>A) is classified Likely benign in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-06). Very rare (popmax 0.00439%, sas); Associated with dystonic disorder.

What condition is associated with GNAL p.Pro425= (c.1275G>A)?

GNAL p.Pro425= (c.1275G>A) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Pro425= (c.1275G>A) in the general population?

GNAL p.Pro425= (c.1275G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

GNAL p.Pro425=

c.1275G>A · rs780742831 · VCV1159406

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 -9.6	GERP -3.7
Overall
CADD	0.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,072 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000991% 16/1,613,946 alleles · very rare exomes 14/1,461,808 · genomes 2/152,138 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,768
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000847%	117,999

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.Pro425=
Coding: c.1275G>A
MANE Select: NM_182978
dbSNP: rs780742831
Type: single nucleotide variant
Location: chr18:11881033 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB

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.Pro425Gln 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
GNAL c.1163-7T>G 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-pro425 (accessed [today's date]).

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