Is RASA1 p.Pro697Ala (c.2089C>G) pathogenic?

RASA1 p.Pro697Ala (c.2089C>G) is classified Uncertain significance in RASA1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-18). AlphaMissense: likely benign (0.1932); Very rare (popmax 0.00534%, nfe); Associated with capillary malformation-arteriovenous malformation 1.

What condition is associated with RASA1 p.Pro697Ala (c.2089C>G)?

RASA1 p.Pro697Ala (c.2089C>G) is associated with capillary malformation-arteriovenous malformation 1, capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro697Ala (c.2089C>G) in the general population?

RASA1 p.Pro697Ala (c.2089C>G) is very rare (popmax 0.00534%, nfe) (gnomAD).

How is Parkes Weber syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RASA1 p.Pro697Ala (c.2089C>G)?

AlphaMissense predicts likely benign (score 0.1932) — an in-silico prediction, not a clinical call.

RASA1 p.Pro697Ala

c.2089C>G · rs759711265 · VCV907944

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

capillary malformation-arteriovenous malformation 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1932	likely benign
REVEL	0.52	indeterminate
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 0.00534% European (non-Finnish) · 63/1,179,978 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00409% 66/1,613,860 alleles · very rare exomes 61/1,461,734 · genomes 5/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,730
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00134%	74,884

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: RASA1
Protein: p.Pro697Ala
Coding: c.2089C>G
MANE Select: NM_002890
dbSNP: rs759711265
Type: single nucleotide variant
Location: chr5:87376470 (GRCh38)

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

Disease context

capillary malformation-arteriovenous malformation 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: capillary malformation-arteriovenous malformation syndrome

For Parkes Weber syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Infancy, Neonatal

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-pro697ala (accessed [today's date]).

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