Is GRIN3A p.Pro20Ser (c.58C>T) pathogenic?

GRIN3A p.Pro20Ser (c.58C>T) is classified Uncertain significance in GRIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1189); Very rare (popmax 0.00777%, amr).

How common is GRIN3A p.Pro20Ser (c.58C>T) in the general population?

GRIN3A p.Pro20Ser (c.58C>T) is very rare (popmax 0.00777%, amr) (gnomAD).

What do computational predictors say about GRIN3A p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.1189) — an in-silico prediction, not a clinical call.

GRIN3A p.Pro20Ser

c.58C>T · rs957551703 · VCV2466820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00777%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1189	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -6.38	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 165 kb · p 0.064 · regional, not allelic
Overall
CADD	23.9	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 0.00777% Admixed American · 4/51,492 alleles

Filtering AF 0.00261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00152%

Overall 0.00163% 25/1,536,754 alleles · very rare exomes 22/1,384,560 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00777%	12,873
South Asian	0.00238%	42,075
European (non-Finnish)	0.00157%	63,774
African / African-American	0.00137%	73,194

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: GRIN3A
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_133445
dbSNP: rs957551703
Type: single nucleotide variant
Location: chr9:101737922 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.24 · 3 PDB

Full GRIN3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPP3R2 p.Ile20Thr Uncertain significance ★ ⚠ same residue
GRIN3A p.Asn1062Ser Benign ★★ same type
GRIN3A p.Phe1029Leu Likely benign ★★ same type
GRIN3A p.Ala1096Ser Uncertain significance ★ ⚠ same type
GRIN3A p.Ala127Thr Uncertain significance ★ ⚠ same type
GRIN3A p.Ala22Val Uncertain significance ★ ⚠ same type
GRIN3A p.Ala299Ser Uncertain significance ★ ⚠ same type
GRIN3A p.Ala397Thr 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/grin3a-p-pro20ser (accessed [today's date]).

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