Is GABRB3 p.Pro25= (c.75C>T) pathogenic?

GABRB3 p.Pro25= (c.75C>T) is classified Benign in GABRB3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Common (popmax 36.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with epilepsy, childhood absence, susceptibility to, 1.

What condition is associated with GABRB3 p.Pro25= (c.75C>T)?

GABRB3 p.Pro25= (c.75C>T) is associated with epilepsy, childhood absence, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 5 (ClinVar).

GABRB3 p.Pro25=

Q: How common is GABRB3 p.Pro25= (c.75C>T) in the general population?

GABRB3 p.Pro25= (c.75C>T) is common (popmax 36.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.75C>T · rs20318 · VCV377904

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 36.6%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

epilepsy, childhood absence, susceptibility to, 1

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 2.8	GERP -1.3, phastCons 1
Overall
CADD	17.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.6% Admixed American · 19,259/52,624 alleles

Filtering AF 36.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 36%

Overall 17.5% 274,088/1,562,694 alleles · common exomes 250,332/1,410,666 · genomes 23,756/152,028 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	36.6%	3
East Asian	33.4%	3
South Asian	22.3%	4
Finnishnot grpmax-eligible	19.9%	5
Remaining individualsnot grpmax-eligible	17.2%	6
European (non-Finnish)	16.7%	6
Amishnot grpmax-eligible	16.7%	6
Middle Eastern	13.4%	7
Ashkenazi Jewishnot grpmax-eligible	12.8%	8
African / African-American	3.49%	29

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: GABRB3
Protein: p.Pro25=
Coding: c.75C>T
MANE Select: NM_000814 · reported on NM_021912
dbSNP: rs20318
Type: single nucleotide variant
Location: chr15:26773650 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.64 · 109 PDB

Full GABRB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, childhood absence, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy, childhood absence, susceptibility to, 5

Similar variants

GABRB3 p.Ala25Ser Uncertain significance ★★ ⚠ same residue
GABRB3 p.Ala25Thr Likely benign ★ same residue
GABRB3 p.Arg111Ter Pathogenic ★★ same condition
GABRB3 p.Arg194Ter Pathogenic ★★ same condition
GABRB3 p.Arg232Gln Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Arg96Ser Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Asp120Asn Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Glu77Gln Likely 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/gabrb3-p-pro25 (accessed [today's date]).

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