Is RASA1 p.Pro139Arg (c.416C>G) pathogenic?

RASA1 p.Pro139Arg (c.416C>G) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-13). AlphaMissense: likely benign (0.1763); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Pro139Arg (c.416C>G)?

RASA1 p.Pro139Arg (c.416C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is RASA1 p.Pro139Arg (c.416C>G) in the general population?

RASA1 p.Pro139Arg (c.416C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASA1 p.Pro139Arg (c.416C>G)?

AlphaMissense predicts likely benign (score 0.1763) — an in-silico prediction, not a clinical call.

RASA1 p.Pro139Arg

c.416C>G · VCV4150719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1763 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1763	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.56, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 63 kb · p 0.0025 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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: RASA1
Protein: p.Pro139Arg
Coding: c.416C>G
MANE Select: NM_002890
Type: single nucleotide variant
Location: chr5:87268867 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 15 PDB

Full RASA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RASA1 p.Pro139Ala Uncertain significance ★ ⚠ same residue
RASA1 p.Pro139= Likely benign ★ same residue
RASA1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala32Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala96Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Gly133Asp Uncertain significance ★★ ⚠ same condition
RASA1 p.Gly151Arg Uncertain significance ★★ same condition
RASA1 p.Gly85Ala 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/rasa1-p-pro139arg (accessed [today's date]).

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