Is GABRR3 p.Phe5Ser (c.14T>C) pathogenic?

GABRR3 p.Phe5Ser (c.14T>C) is classified Likely benign in GABRR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0846); Very rare (popmax 8.48e-05%, nfe).

How common is GABRR3 p.Phe5Ser (c.14T>C) in the general population?

GABRR3 p.Phe5Ser (c.14T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about GABRR3 p.Phe5Ser (c.14T>C)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

GABRR3 p.Phe5Ser

c.14T>C · VCV4261213

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.36	GERP -2.5
Overall
CADD	4.392	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,092 alleles

Overall 6.2e-05% 1/1,612,654 alleles · very rare exomes 1/1,460,370 · genomes 0/152,284 · joint denominator

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.Phe5Ser
Coding: c.14T>C
MANE Select: NM_001105580
Type: single nucleotide variant
Location: chr3:98034974 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.27

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-phe5ser (accessed [today's date]).

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