Is RRAS p.Pro136= (c.408C>G) pathogenic?

RRAS p.Pro136= (c.408C>G) is classified Likely benign in RRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-11). Absent from gnomAD v4.1; Associated with Noonan syndrome.

What condition is associated with RRAS p.Pro136= (c.408C>G)?

RRAS p.Pro136= (c.408C>G) is associated with Noonan syndrome (ClinVar).

How common is RRAS p.Pro136= (c.408C>G) in the general population?

RRAS p.Pro136= (c.408C>G) is absent from gnomAD v4.1 (gnomAD).

RRAS p.Pro136=

c.408C>G · rs114187560 · VCV1130294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.49	GERP -3.7
Overall
CADD	1.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RRAS
Protein: p.Pro136=
Coding: c.408C>G
MANE Select: NM_006270
dbSNP: rs114187560
Type: single nucleotide variant
Location: chr19:49636664 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB

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.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
RRAS p.Arg113Gln Uncertain significance ★★ ⚠ same condition
RRAS p.Arg128Gln Uncertain significance ★★ ⚠ same condition
RRAS p.Arg132Cys Uncertain significance ★★ same condition
RRAS p.Arg132His 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-pro136 (accessed [today's date]).

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