Is RRAS p.Phe54= (c.162C>T) pathogenic?

RRAS p.Phe54= (c.162C>T) is classified Likely benign in RRAS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-30). Ultra-rare (popmax 0.012%, afr); Associated with Noonan syndrome.

What condition is associated with RRAS p.Phe54= (c.162C>T)?

RRAS p.Phe54= (c.162C>T) is associated with Noonan syndrome (ClinVar).

How common is RRAS p.Phe54= (c.162C>T) in the general population?

RRAS p.Phe54= (c.162C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

RRAS p.Phe54=

c.162C>T · rs751721094 · VCV1776790

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, 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 -0.27	GERP -3.4, phastCons 0.01
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,850 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00118% 19/1,612,332 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,317
Admixed American	0.00334%	29,921
South Asian	0.0011%	90,860
European (non-Finnish)	0.000593%	168,501

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.Phe54=
Coding: c.162C>T
MANE Select: NM_006270
dbSNP: rs751721094
Type: single nucleotide variant
Location: chr19:49637122 (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-phe54 (accessed [today's date]).

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