Is RRAS p.Val137= (c.411T>C) pathogenic?

RRAS p.Val137= (c.411T>C) is classified Likely benign in RRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). Very rare (popmax 8.47e-05%, nfe).

How common is RRAS p.Val137= (c.411T>C) in the general population?

RRAS p.Val137= (c.411T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RRAS p.Val137=

c.411T>C · VCV3435496

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 -2.3	GERP -3.7
Overall
CADD	0.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,980 alleles

Overall 6.2e-05% 1/1,614,102 alleles · very rare exomes 1/1,461,836 · genomes 0/152,266 · 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: RRAS
Protein: p.Val137=
Coding: c.411T>C
MANE Select: NM_006270
Type: single nucleotide variant
Location: chr19:49636661 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB
Residue 137: a β-strand

Full RRAS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RRAS p.Val137Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
RRAS p.Ala109Thr Uncertain significance ★★ ⚠ same type
RRAS p.Ala162Thr Uncertain significance ★★ ⚠ same type
RRAS p.Ala205Val Uncertain significance ★★ ⚠ same type
RRAS p.Ala85Val Uncertain significance ★★ ⚠ same type
RRAS p.Arg113Gln Uncertain significance ★★ ⚠ same type
RRAS p.Arg128Gln Uncertain significance ★★ ⚠ same type
RRAS p.Arg132Cys 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/rras-p-val137 (accessed [today's date]).

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