Is RRAS p.Arg15= (c.43C>A) pathogenic?

RRAS p.Arg15= (c.43C>A) is classified Likely benign in RRAS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-03). Rare (popmax 0.143%, sas); Associated with Noonan syndrome.

What condition is associated with RRAS p.Arg15= (c.43C>A)?

RRAS p.Arg15= (c.43C>A) is associated with Noonan syndrome (ClinVar).

How common is RRAS p.Arg15= (c.43C>A) in the general population?

RRAS p.Arg15= (c.43C>A) is rare (popmax 0.143%, sas) (gnomAD).

RRAS p.Arg15=

c.43C>A · rs544651800 · VCV1646121

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.143%, sas)

Conditions

Noonan syndrome

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 3.7	GERP 0.21, phastCons 1
Overall
CADD	14.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% South Asian · 113/79,068 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.0078% 116/1,487,782 alleles · rare exomes 113/1,335,690 · genomes 3/152,092 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.143%	700
Remaining individualsnot grpmax-eligible	0.00348%	28,741
African / African-American	0.00146%	68,662

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.Arg15=
Coding: c.43C>A
MANE Select: NM_006270
dbSNP: rs544651800
Type: single nucleotide variant
Location: chr19:49640056 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB
Residue 15: the 'disordered' region

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

Disease context

Noonan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RRAS p.Arg15Pro Uncertain significance ★★ ⚠ same residue
RRAS p.Arg15Gln Uncertain significance ★ ⚠ same residue
RRAS p.Arg15Gly Uncertain significance ★ ⚠ same residue
RRAS p.Arg15Trp Uncertain significance ★ ⚠ same residue
RRAS p.Ala109Thr Uncertain significance ★★ ⚠ same condition
RRAS p.Ala162Thr Uncertain significance ★★ ⚠ same condition
RRAS p.Ala205Val Uncertain significance ★★ ⚠ same condition
RRAS p.Ala85Val 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/rras-p-arg15 (accessed [today's date]).

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