GRIN2C p.Arg435=
c.1305G>A · rs61741745 · VCV780168
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.03%, afr)
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 0.58 | phastCons 1 |
| Overall | ||
| CADD | 10.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.03%
African / African-American · 2,273/75,018 alleles
Filtering AF
2.93%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.88%
Overall
0.185%
2,981/1,613,638 alleles · low-frequency
exomes 1,707/1,461,370 · genomes 1,274/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.03% | 33 |
| Middle Eastern | 0.511% | 196 |
| Admixed American | 0.287% | 349 |
| Remaining individualsnot grpmax-eligible | 0.283% | 353 |
| Ashkenazi Jewishnot grpmax-eligible | 0.108% | 925 |
| European (non-Finnish) | 0.0242% | 4,140 |
| South Asian | 0.0121% | 8,280 |
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
- GRIN2C
- Protein
- p.Arg435=
- Coding
- c.1305G>A
- MANE Select
- NM_000835
- dbSNP
- rs61741745
- Type
- single nucleotide variant
- Location
- chr17:74850576 (GRCh38)
- Gene constraint
- LOEUF 1.163 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 6 PDB
- Residue 435
- a UniProt-annotated variant site (found in a patient with autism spectrum disorder; uncertain significance)
Similar variants
- GRIN2C p.Arg435Met Uncertain significance ★ ⚠ same residue
- GRIN2C p.Ala8Thr Likely benign ★★ same type
- GRIN2C p.Ala999= Likely benign ★★ same type
- GRIN2C p.Arg401Gln Benign ★★ same type
- GRIN2C p.Ile519= Benign/Likely benign ★★ same type
- GRIN2C p.Leu65Phe Likely benign ★★ same type
- GRIN2C p.Thr1196Ile Benign ★★ same type
- GRIN2C p.Val191Ala Likely benign ★★ 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/grin2c-p-arg435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown