Is GLRA2 p.Phe47Ser (c.140T>C) pathogenic?

GLRA2 p.Phe47Ser (c.140T>C) is classified Likely pathogenic in GLRA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-10). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1.

How common is GLRA2 p.Phe47Ser (c.140T>C) in the general population?

GLRA2 p.Phe47Ser (c.140T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLRA2 p.Phe47Ser (c.140T>C)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

GLRA2 p.Phe47Ser

c.140T>C · rs2146999184 · VCV1334140

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9985	likely pathogenic ✓ concordant with ClinVar · top 10% in GLRA2
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -12.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.4, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 159 kb · p 9e-16 · regional, not allelic
Overall
CADD	28.9	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: GLRA2
Protein: p.Phe47Ser
Coding: c.140T>C
MANE Select: NM_002063
dbSNP: rs2146999184
Type: single nucleotide variant
Location: chrX:14532310 (GRCh38)
Structure: AlphaFold pLDDT 84.04 · 13 PDB
Residue 47: a UniProt-annotated variant site (in mrxsp; uncertain significance)

Full GLRA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GLRA2 p.Thr296Met Pathogenic ★★ same type
GLRA2 p.Arg252Cys Uncertain significance ★★ ⚠ same type
GLRA2 p.Leu166Val Uncertain significance ★★ same type
GLRA2 p.Ser39Pro Uncertain significance ★★ ⚠ same type
GLRA2 p.Arg165Thr Likely pathogenic ★ same type
GLRA2 p.Asp131Gly Likely pathogenic ★ same type
GLRA2 p.Ile259Met Likely pathogenic ★ same type
GLRA2 c.202+4G>T 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/glra2-p-phe47ser (accessed [today's date]).

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