Is GRIN2D p.Pro707Ser (c.2119C>T) pathogenic?

GRIN2D p.Pro707Ser (c.2119C>T) is classified Uncertain significance in GRIN2D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-22). AlphaMissense: likely pathogenic (0.6259); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Pro707Ser (c.2119C>T)?

GRIN2D p.Pro707Ser (c.2119C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Pro707Ser (c.2119C>T) in the general population?

GRIN2D p.Pro707Ser (c.2119C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about GRIN2D p.Pro707Ser (c.2119C>T)?

AlphaMissense predicts likely pathogenic (score 0.6259) — an in-silico prediction, not a clinical call.

GRIN2D p.Pro707Ser

c.2119C>T · rs762071940 · VCV1929078

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6259 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6259	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 23 kb · p 8.9e-16 · regional, not allelic
Overall
CADD	29.0	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,988 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,826 alleles · very rare

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: GRIN2D
Protein: p.Pro707Ser
Coding: c.2119C>T
MANE Select: NM_000836
dbSNP: rs762071940
Type: single nucleotide variant
Location: chr19:48421812 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB

Full GRIN2D 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

GRIN2D p.Pro707Thr Uncertain significance ★ ⚠ same residue
GRIN2D p.Ala1032Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1135Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1208Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1244Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1256Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1310Gly Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala149Val 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/grin2d-p-pro707ser (accessed [today's date]).

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