Is GRIN3B p.Pro276Ser (c.826C>T) pathogenic?

GRIN3B p.Pro276Ser (c.826C>T) is classified Uncertain significance in GRIN3B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-10). AlphaMissense: likely benign (0.0994); Very rare (popmax 0.000437%, nfe).

How common is GRIN3B p.Pro276Ser (c.826C>T) in the general population?

GRIN3B p.Pro276Ser (c.826C>T) is very rare (popmax 0.000437%, nfe) (gnomAD).

What do computational predictors say about GRIN3B p.Pro276Ser (c.826C>T)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

GRIN3B p.Pro276Ser

c.826C>T · rs1309414183 · VCV2482698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000437%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -8.34	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 3	GERP 0.97, phastCons 0.054
Regional constraint	o/e 1.14	unconstrained · MANE · 9,161 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	19.75	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000437% European (non-Finnish) · 5/1,142,856 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000327% 5/1,528,692 alleles · very rare exomes 5/1,376,354 · genomes 0/152,338 · 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: GRIN3B
Protein: p.Pro276Ser
Coding: c.826C>T
MANE Select: NM_138690
dbSNP: rs1309414183
Type: single nucleotide variant
Location: chr19:1003529 (GRCh38)
Gene constraint: LOEUF 1.754 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 75.35

Full GRIN3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRIN3B c.-17A>G Benign ★★ same type
GRIN3B p.Ala403= Benign ★★ same type
GRIN3B p.Glu852Lys Benign ★★ same type
GRIN3B p.His117Tyr Benign ★★ same type
GRIN3B p.Pro1039Arg Benign ★★ same type
GRIN3B p.Thr562= Benign ★★ same type
GRIN3B p.Thr577Met Benign ★★ same type
GRIN3B p.Ala1025Gly 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/grin3b-p-pro276ser (accessed [today's date]).

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