Is RRAS p.Ser3Arg (c.9C>G) pathogenic?

RRAS p.Ser3Arg (c.9C>G) is classified Uncertain significance in RRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: ambiguous (0.3548); No allele count reported in gnomAD v4.1 (AN 1,395,176); Associated with RRAS-related disorder.

What condition is associated with RRAS p.Ser3Arg (c.9C>G)?

RRAS p.Ser3Arg (c.9C>G) is associated with RRAS-related disorder (ClinVar).

How common is RRAS p.Ser3Arg (c.9C>G) in the general population?

RRAS p.Ser3Arg (c.9C>G) is no allele count reported in gnomAD v4.1 (AN 1,395,176) (gnomAD).

What do computational predictors say about RRAS p.Ser3Arg (c.9C>G)?

AlphaMissense predicts ambiguous (score 0.3548) — an in-silico prediction, not a clinical call.

RRAS p.Ser3Arg

c.9C>G · rs2081015859 · VCV2631818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3548 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,395,176)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

RRAS-related disorder

Computational evidence

Protein change
AlphaMissense	0.3548	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.46	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.19, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,519 bp · p 0.14 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,395,176). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RRAS
Protein: p.Ser3Arg
Coding: c.9C>G
MANE Select: NM_006270
dbSNP: rs2081015859
Type: single nucleotide variant
Location: chr19:49640090 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB
Residue 3: the 'disordered' region

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

Disease context

RRAS-related disorder

Similar variants

RRAS p.Ser56Cys Uncertain significance ★★ ⚠ same condition
RRAS p.Ser27= Conflicting classifications of pathogenicity ★ same condition
RRAS p.Arg13= Likely benign same condition
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

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-ser3arg (accessed [today's date]).

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