Is GNAO1 p.Asp299= (c.897C>T) pathogenic?

GNAO1 p.Asp299= (c.897C>T) is classified Likely benign in GNAO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Ultra-rare (popmax 0.0144%, nfe); Associated with early-infantile DEE.

What condition is associated with GNAO1 p.Asp299= (c.897C>T)?

GNAO1 p.Asp299= (c.897C>T) is associated with early-infantile DEE (ClinVar).

How common is GNAO1 p.Asp299= (c.897C>T) in the general population?

GNAO1 p.Asp299= (c.897C>T) is ultra-rare (popmax 0.0144%, nfe) (gnomAD).

GNAO1 p.Asp299=

c.897C>T · rs148878451 · VCV706511

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, nfe)

Conditions

early-infantile DEE

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 -2.5	GERP -3.9
Overall
CADD	5.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0144% European (non-Finnish) · 170/1,178,754 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0113% 182/1,612,414 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0144%	6,934
Remaining individualsnot grpmax-eligible	0.00641%	15,608
South Asian	0.0044%	22,749
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,568
East Asian	0.00223%	44,854
Finnishnot grpmax-eligible	0.00156%	63,898
African / African-American	0.00133%	74,962

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: GNAO1
Protein: p.Asp299=
Coding: c.897C>T
MANE Select: NM_020988
dbSNP: rs148878451
Type: single nucleotide variant
Location: chr16:56354885 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 94.67 · 89 PDB
Residue 299: the g-alpha domain; an α-helix

Full GNAO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNAO1 c.723+1G>A Pathogenic ★★ same condition
GNAO1 c.724-8G>A Pathogenic/Likely pathogenic ★★ same condition
GNAO1 p.Ala227Val Pathogenic/Likely pathogenic ★★ same condition
GNAO1 p.Arg206Leu Pathogenic/Likely pathogenic ★★ same condition
GNAO1 p.Arg209Cys Pathogenic ★★ same condition
GNAO1 p.Arg209His Pathogenic ★★ same condition
GNAO1 p.Arg209Leu Pathogenic/Likely pathogenic ★★ same condition
GNAO1 p.Gln52Arg Pathogenic ★★ 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/gnao1-p-asp299 (accessed [today's date]).

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