Is RRAS p.Pro24Ser (c.70C>T) pathogenic?

RRAS p.Pro24Ser (c.70C>T) is classified Uncertain significance in RRAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.073); No allele count reported in gnomAD v4.1 (AN 1,548,110); Associated with Noonan syndrome.

What condition is associated with RRAS p.Pro24Ser (c.70C>T)?

RRAS p.Pro24Ser (c.70C>T) is associated with Noonan syndrome (ClinVar).

How common is RRAS p.Pro24Ser (c.70C>T) in the general population?

RRAS p.Pro24Ser (c.70C>T) is no allele count reported in gnomAD v4.1 (AN 1,548,110) (gnomAD).

What do computational predictors say about RRAS p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

RRAS p.Pro24Ser

c.70C>T · rs2122429906 · VCV1492900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,110)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Noonan syndrome

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -11.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.4	GERP -1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,519 bp · p 0.14 · regional, not allelic
Overall
CADD	24.3	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 1,548,110). 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.Pro24Ser
Coding: c.70C>T
MANE Select: NM_006270
dbSNP: rs2122429906
Type: single nucleotide variant
Location: chr19:49640029 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.79 · 2 PDB
Residue 24: an α-helix; 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.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-pro24ser (accessed [today's date]).

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