Is GNAL p.Ser248= (c.744C>T) pathogenic?

GNAL p.Ser248= (c.744C>T) is classified Benign in GNAL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-16). Rare (popmax 0.245%, sas); Associated with dystonic disorder.

What condition is associated with GNAL p.Ser248= (c.744C>T)?

GNAL p.Ser248= (c.744C>T) is associated with dystonic disorder (ClinVar).

How common is GNAL p.Ser248= (c.744C>T) in the general population?

GNAL p.Ser248= (c.744C>T) is rare (popmax 0.245%, sas) (gnomAD).

GNAL p.Ser248=

c.744C>T · rs368148399 · VCV701450

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.245%, 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 -12	GERP -3.7
Overall
CADD	2.705	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.245% South Asian · 223/91,064 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.208%

Overall 0.0164% 264/1,613,564 alleles · rare exomes 235/1,461,316 · genomes 29/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.245%	408
Remaining individualsnot grpmax-eligible	0.032%	3,124
African / African-American	0.02%	5,001
East Asian	0.00223%	44,876
European (non-Finnish)	0.000424%	235,907

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.Ser248=
Coding: c.744C>T
MANE Select: NM_182978
dbSNP: rs368148399
Type: single nucleotide variant
Location: chr18:11862416 (GRCh38)
Gene constraint: LOEUF 1.72 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.46 · 10 PDB
Residue 248: 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-ser248 (accessed [today's date]).

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