Is GABBR2 p.Pro20Ser (c.58C>T) pathogenic?

GABBR2 p.Pro20Ser (c.58C>T) is classified Conflicting classifications of pathogenicity in GABBR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-09). AlphaMissense: likely benign (0.0923); Very rare (popmax 0.00638%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GABBR2 p.Pro20Ser (c.58C>T)?

GABBR2 p.Pro20Ser (c.58C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GABBR2 p.Pro20Ser (c.58C>T) in the general population?

GABBR2 p.Pro20Ser (c.58C>T) is very rare (popmax 0.00638%, nfe) (gnomAD).

What do computational predictors say about GABBR2 p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

GABBR2 p.Pro20Ser

c.58C>T · rs1430262254 · VCV949372

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00638%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -8.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP 1, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 164 bp · p 0.69 · regional, not allelic
Overall
CADD	18.35	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

Grpmax group 0.00638% European (non-Finnish) · 57/893,042 alleles

Filtering AF 0.00499% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00537% 58/1,080,878 alleles · very rare exomes 53/933,692 · genomes 5/147,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00638%	15,667
Remaining individualsnot grpmax-eligible	0.00282%	35,484

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: GABBR2
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_005458
dbSNP: rs1430262254
Type: single nucleotide variant
Location: chr9:98708680 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB

Full GABBR2 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

GABBR2 p.Pro20= Likely benign ★ same residue
GABBR2 p.Ala570Thr Uncertain significance ★★ ⚠ same condition
GABBR2 p.Ala912Thr Uncertain significance ★★ ⚠ same condition
GABBR2 p.Arg197Cys Uncertain significance ★★ ⚠ same condition
GABBR2 p.Arg799Gln Uncertain significance ★★ same condition
GABBR2 p.Gln194His Uncertain significance ★★ ⚠ same condition
GABBR2 p.Glu320Gln Uncertain significance ★★ same condition
GABBR2 p.Gly671Ser 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/gabbr2-p-pro20ser (accessed [today's date]).

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