Is GRIN1 p.Pro516= (c.1548G>A) pathogenic?

GRIN1 p.Pro516= (c.1548G>A) is classified Benign in GRIN1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.47%, eas); Associated with Inborn genetic diseases.

What condition is associated with GRIN1 p.Pro516= (c.1548G>A)?

GRIN1 p.Pro516= (c.1548G>A) is associated with Inborn genetic diseases, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (ClinVar).

How common is GRIN1 p.Pro516= (c.1548G>A) in the general population?

GRIN1 p.Pro516= (c.1548G>A) is low-frequency (popmax 3.47%, eas) (gnomAD).

GRIN1 p.Pro516=

c.1548G>A · rs75783429 · VCV383643

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.47%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -3.7
Overall
CADD	4.817	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.47% East Asian · 1,444/41,606 alleles

Filtering AF 3.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.26%

Overall 0.35% 5,459/1,557,628 alleles · low-frequency exomes 4,507/1,405,556 · genomes 952/152,072 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	3.47%	29
South Asian	2.52%	40
African / African-American	1.31%	76
Remaining individualsnot grpmax-eligible	0.611%	164
Middle Eastern	0.384%	260
Admixed American	0.156%	642
Ashkenazi Jewishnot grpmax-eligible	0.143%	700
European (non-Finnish)	0.0349%	2,863

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: GRIN1
Protein: p.Pro516=
Coding: c.1548G>A
MANE Select: NM_007327
dbSNP: rs75783429
Type: single nucleotide variant
Location: chr9:137162004 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 516: the 'disordered' region

Full GRIN1 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

Also linked: neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Similar variants

GPRIN1 p.Gly516Ala Uncertain significance ★ ⚠ same residue
GRIN1 p.Arg659Gln Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg659Trp Pathogenic ★★ same condition
GRIN1 p.Arg794Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GRIN1 p.Arg844Cys Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg844Leu Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Asp227His Likely pathogenic ★★ same condition
GRIN1 p.Asp732Glu Pathogenic/Likely pathogenic ★★ 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/grin1-p-pro516 (accessed [today's date]).

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