Is GABRR3 p.Ser285Pro (c.853T>C) pathogenic?

GABRR3 p.Ser285Pro (c.853T>C) is classified Uncertain significance in GABRR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-21). AlphaMissense: likely pathogenic (0.8807); Very rare (popmax 0.00501%, amr).

How common is GABRR3 p.Ser285Pro (c.853T>C) in the general population?

GABRR3 p.Ser285Pro (c.853T>C) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about GABRR3 p.Ser285Pro (c.853T>C)?

AlphaMissense predicts likely pathogenic (score 0.8807) — an in-silico prediction, not a clinical call.

GABRR3 p.Ser285Pro

c.853T>C · VCV4670473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.8807	likely pathogenic · top 8% in GABRR3
SaProt	LLR -15.48	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.52, phastCons 0.56
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00501% Admixed American · 3/59,916 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,382 alleles · very rare exomes 4/1,461,104 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,972
European (non-Finnish)	8.48e-05%	1,179,490

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: GABRR3
Protein: p.Ser285Pro
Coding: c.853T>C
MANE Select: NM_001105580
Type: single nucleotide variant
Location: chr3:98001669 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.27
Residue 285: a UniProt-annotated variant site (in)

Full GABRR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GABRR3 p.Ala241Glu Uncertain significance ★ same type
GABRR3 p.Ala246Ser Uncertain significance ★ ⚠ same type
GABRR3 p.Ala319Thr Uncertain significance ★ ⚠ same type
GABRR3 p.Ala4Asp Uncertain significance ★ ⚠ same type
GABRR3 p.Ala73Ser Uncertain significance ★ ⚠ same type
GABRR3 p.Arg111Thr Uncertain significance ★ ⚠ same type
GABRR3 p.Arg118Lys Uncertain significance ★ same type
GABRR3 p.Arg165Cys Uncertain significance ★ ⚠ 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/gabrr3-p-ser285pro (accessed [today's date]).

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