NRAS p.Asp175=
c.525T>C · rs1057524394 · VCV392204
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000594%, nfe)
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 0.63 | GERP 0.081, phastCons 0.88 |
| Overall | ||
| CADD | 7.948 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000594%
European (non-Finnish) · 7/1,179,402 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000479%
7/1,461,184 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
- NRAS
- Protein
- p.Asp175=
- Coding
- c.525T>C
- MANE Select
- NM_002524
- dbSNP
- rs1057524394
- Type
- single nucleotide variant
- Location
- chr1:114708580 (GRCh38)
- Gene constraint
- LOEUF 0.55 · pLI 0.94 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.56 · 36 PDB
- Residue 175
- the 'hypervariable region' region
Similar variants
- NRAS p.Gly12Ser Pathogenic ★★★ same type
- NRAS p.Gly60Glu Pathogenic ★★★ same type
- NRAS p.Ile24Asn Likely pathogenic ★★★ same type
- NRAS p.Thr50Ile Pathogenic ★★★ same type
- NRAS p.Thr58Ile Pathogenic ★★★ same type
- NRAS p.Ala11Thr Uncertain significance ★★★ ⚠ same type
- NRAS p.Ala91Val Uncertain significance ★★★ ⚠ same type
- NRAS p.Arg123Lys Uncertain significance ★★★ ⚠ 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/nras-p-asp175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown