Is GNAL p.Ser23= (c.69G>A) pathogenic?

GNAL p.Ser23= (c.69G>A) is classified Uncertain significance in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-06). Very rare (popmax 0.000373%, nfe); Associated with dystonic disorder.

What condition is associated with GNAL p.Ser23= (c.69G>A)?

GNAL p.Ser23= (c.69G>A) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Ser23= (c.69G>A) in the general population?

GNAL p.Ser23= (c.69G>A) is very rare (popmax 0.000373%, nfe) (gnomAD).

GNAL p.Ser23=

c.69G>A · rs987117042 · VCV526210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000373%, nfe)

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 1.1	GERP -1.1, phastCons 0.82
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000373% European (non-Finnish) · 4/1,071,316 alleles

Filtering AF 8.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.9e-05%

Overall 0.000292% 4/1,369,188 alleles · very rare exomes 2/1,217,366 · genomes 2/151,822 · 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.Ser23=
Coding: c.69G>A
MANE Select: NM_182978
dbSNP: rs987117042
Type: single nucleotide variant
Location: chr18:11689632 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 23: the 'disordered' 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-ser23 (accessed [today's date]).

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