NRAS p.Ile100=
c.300T>A · rs575693594 · VCV764200
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
Conditions
1
RASopathy
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 2.6 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 9.371 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,054 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00112%
18/1,612,966 alleles · ultra-rare
exomes 18/1,460,712 · genomes 0/152,254 · joint denominator
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
- NRAS
- Protein
- p.Ile100=
- Coding
- c.300T>A
- MANE Select
- NM_002524
- dbSNP
- rs575693594
- Type
- single nucleotide variant
- Location
- chr1:114709719 (GRCh38)
- Gene constraint
- LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.56 · 36 PDB
- Residue 100
- an α-helix
Similar variants
- NRAS p.Ile100Met Uncertain significance ★ ⚠ same residue
- NRAS p.Ile100Thr Uncertain significance ★ ⚠ same residue
- NRAS p.Gly12Ser Pathogenic ★★★ same condition
- NRAS p.Gly60Glu Pathogenic ★★★ same condition
- NRAS p.Ile24Asn Likely pathogenic ★★★ same condition
- NRAS p.Thr50Ile Pathogenic ★★★ same condition
- NRAS p.Thr58Ile Pathogenic ★★★ same condition
- NRAS p.Ala11Thr 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/nras-p-ile100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown