Is GABBR1 p.Pro153Arg (c.458C>G) pathogenic?

GABBR1 p.Pro153Arg (c.458C>G) is classified Uncertain significance in GABBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-11). AlphaMissense: likely benign (0.0956); Absent from gnomAD v4.1.

How common is GABBR1 p.Pro153Arg (c.458C>G) in the general population?

GABBR1 p.Pro153Arg (c.458C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABBR1 p.Pro153Arg (c.458C>G)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

GABBR1 p.Pro153Arg

c.458C>G · VCV3852429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 17 kb · p 1.8e-28 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: GABBR1
Protein: p.Pro153Arg
Coding: c.458C>G
MANE Select: NM_001470
Type: single nucleotide variant
Location: chr6:29630475 (GRCh38)
Gene constraint: LOEUF 0.378 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 24 PDB
Residue 153: the sushi 2 domain; a disulfide bond

Full GABBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GABBR1 p.Gly531Ser Pathogenic/Likely pathogenic ★★ same type
GABBR1 p.Ala712Thr Uncertain significance ★★ ⚠ same type
GABBR1 p.Ala726Val Uncertain significance ★★ ⚠ same type
GABBR1 p.Arg13Cys Uncertain significance ★★ ⚠ same type
GABBR1 p.Arg511Gly Uncertain significance ★★ ⚠ same type
GABBR1 p.Ile754Val Uncertain significance ★★ ⚠ same type
GABBR1 c.964-9C>T Likely benign ★★ same type
GABBR1 p.Arg13= Likely benign ★★ same type

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/gabbr1-p-pro153arg (accessed [today's date]).

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