Is RASA1 p.Pro289Ala (c.865C>G) pathogenic?

RASA1 p.Pro289Ala (c.865C>G) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). AlphaMissense: likely pathogenic (0.9517); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Pro289Ala (c.865C>G)?

RASA1 p.Pro289Ala (c.865C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is RASA1 p.Pro289Ala (c.865C>G) in the general population?

RASA1 p.Pro289Ala (c.865C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASA1 p.Pro289Ala (c.865C>G)?

AlphaMissense predicts likely pathogenic (score 0.9517) — an in-silico prediction, not a clinical call.

RASA1 p.Pro289Ala

c.865C>G · rs2531194891 · VCV3222919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9517 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9517	likely pathogenic
REVEL	0.321	indeterminate
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 5e-15 · regional, not allelic
Overall
CADD	25.0	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

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.Pro289Ala
Coding: c.865C>G
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs2531194891
Type: single nucleotide variant
Location: chr5:87333303 (GRCh38)

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

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-pro289ala (accessed [today's date]).

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