Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 25%, eas) — too common for a highly-penetrant pathogenic allele
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 -4.2 | |
| Overall | ||
| CADD | 5.502 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25%
East Asian · 11,208/44,830 alleles
Filtering AF
24.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 24.5%
Overall
11.2%
179,709/1,607,346 alleles · common
exomes 158,687/1,455,184 · genomes 21,022/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 25% | 4 |
| Middle Eastern | 25% | 4 |
| South Asian | 23.1% | 4 |
| Admixed American | 20.4% | 5 |
| African / African-American | 18% | 6 |
| Remaining individualsnot grpmax-eligible | 13.8% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 12.3% | 8 |
| European (non-Finnish) | 8.8% | 11 |
| Finnishnot grpmax-eligible | 7.08% | 14 |
| Amishnot grpmax-eligible | 5.59% | 18 |
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.Ala33=
- Coding
- c.99C>T
- MANE Select
- NM_000835
- dbSNP
- rs689730
- Type
- single nucleotide variant
- Location
- chr17:74854994 (GRCh38)
- Gene constraint
- LOEUF 1.163 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.06 · 6 PDB
- Residue 33
- a UniProt-annotated variant site (found in a patient with autism spectrum disorder; uncertain significance)
Similar variants
- GRIN2C p.Ala8Thr Likely benign ★★ same type
- GRIN2C p.Ala999= Likely benign ★★ same type
- GRIN2C p.Arg401Gln Benign ★★ same type
- GRIN2C p.Arg435= 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-ala33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown