Is GLRA2 p.Pro400Ser (c.1198C>T) pathogenic?

GLRA2 p.Pro400Ser (c.1198C>T) is classified Likely benign in GLRA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.0654); Ultra-rare (popmax 0.0228%, sas); Associated with Inborn genetic diseases.

What condition is associated with GLRA2 p.Pro400Ser (c.1198C>T)?

GLRA2 p.Pro400Ser (c.1198C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GLRA2 p.Pro400Ser (c.1198C>T) in the general population?

GLRA2 p.Pro400Ser (c.1198C>T) is ultra-rare (popmax 0.0228%, sas) (gnomAD).

What do computational predictors say about GLRA2 p.Pro400Ser (c.1198C>T)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

GLRA2 p.Pro400Ser

c.1198C>T · VCV4264300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0228%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.286	benign-leaning
SaProt	—	withheld · numbering disagrees past residue 85 · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 192 bp · p 0.17 · regional, not allelic
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0228% South Asian · 13/56,958 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0107%

Overall 0.00116% 14/1,210,977 alleles · ultra-rare exomes 14/1,097,689 · genomes 0/113,288 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0228%	4,381
East Asian	0.00296%	33,812

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: GLRA2
Protein: p.Pro400Ser
Coding: c.1198C>T
MANE Select: NM_002063
Type: single nucleotide variant
Location: chrX:14730324 (GRCh38)
Structure: AlphaFold pLDDT 84.04 · 13 PDB
Residue 400: a UniProt-annotated variant site (in mrxsp; uncertain significance)

Full GLRA2 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

GLRA2 p.Ser39Pro Uncertain significance ★★ ⚠ same condition
GLRA2 p.Arg3Gln Uncertain significance ★ ⚠ same condition
GLRA2 p.Lys310Gln Uncertain significance ★ ⚠ same condition
GLRA2 p.Phe202Leu Uncertain significance ★ ⚠ same condition
GLRA2 p.Pro38His Uncertain significance ★ ⚠ same condition
GLRA2 p.Pro64Gln Uncertain significance ★ ⚠ same condition
GLRA2 p.Ser275Phe Uncertain significance ★ ⚠ same condition
GLRA2 p.Ser307Pro 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/glra2-p-pro400ser (accessed [today's date]).

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