Is GABRD p.Ser189Pro (c.565T>C) pathogenic?

GABRD p.Ser189Pro (c.565T>C) is classified Uncertain significance in GABRD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: ambiguous (0.4221); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GABRD p.Ser189Pro (c.565T>C)?

GABRD p.Ser189Pro (c.565T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GABRD p.Ser189Pro (c.565T>C) in the general population?

GABRD p.Ser189Pro (c.565T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRD p.Ser189Pro (c.565T>C)?

AlphaMissense predicts ambiguous (score 0.4221) — an in-silico prediction, not a clinical call.

GABRD p.Ser189Pro

c.565T>C · VCV4620547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4221 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4221	ambiguous
REVEL	0.541	indeterminate
SaProt	LLR -8.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 4,715 bp · p 4e-13 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GABRD
Protein: p.Ser189Pro
Coding: c.565T>C
MANE Select: NM_000815
Type: single nucleotide variant
Location: chr1:2028166 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB
Residue 189: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRD p.Ser189= Likely benign ★★ same residue
GABRD p.Pro257Leu Likely pathogenic ★★ same condition
GABRD p.Arg244Trp Uncertain significance ★★ ⚠ same condition
GABRD p.Arg378His Uncertain significance ★★ ⚠ same condition
GABRD p.Arg382His Uncertain significance ★★ ⚠ same condition
GABRD p.Arg408His Uncertain significance ★★ ⚠ same condition
GABRD p.Gln18His Uncertain significance ★★ ⚠ same condition
GABRD p.Gln253Leu Uncertain significance ★★ ⚠ 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/gabrd-p-ser189pro (accessed [today's date]).

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