Is RRAS p.Pro14= (c.42C>T) pathogenic?

RRAS p.Pro14= (c.42C>T) is classified Likely benign in RRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). Very rare (popmax 0.00146%, afr); Associated with Noonan syndrome.

What condition is associated with RRAS p.Pro14= (c.42C>T)?

RRAS p.Pro14= (c.42C>T) is associated with Noonan syndrome (ClinVar).

How common is RRAS p.Pro14= (c.42C>T) in the general population?

RRAS p.Pro14= (c.42C>T) is very rare (popmax 0.00146%, afr) (gnomAD).

RRAS p.Pro14=

c.42C>T · rs1354856207 · VCV1656905

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00146%, afr)

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 6.1	GERP 1.4, phastCons 1
Overall
CADD	15.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00146% African / African-American · 1/68,620 alleles

Overall 6.72e-05% 1/1,487,354 alleles · very rare exomes 1/1,335,270 · genomes 0/152,084 · 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.Pro14=
Coding: c.42C>T
MANE Select: NM_006270
dbSNP: rs1354856207
Type: single nucleotide variant
Location: chr19:49640057 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB
Residue 14: 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.Pro14His Uncertain significance ★ ⚠ same residue
RRAS p.Pro14Leu 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
RRAS p.Arg113Gln Uncertain significance ★★ ⚠ same condition
RRAS p.Arg128Gln 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-pro14 (accessed [today's date]).

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