Is RASA1 p.Pro440= (c.1320T>C) pathogenic?

RASA1 p.Pro440= (c.1320T>C) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-01). Very rare (popmax 0.00668%, amr); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro440= (c.1320T>C)?

RASA1 p.Pro440= (c.1320T>C) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro440= (c.1320T>C) in the general population?

RASA1 p.Pro440= (c.1320T>C) is very rare (popmax 0.00668%, amr) (gnomAD).

RASA1 p.Pro440=

c.1320T>C · rs758200534 · VCV1544350

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.3	GERP 1.5, phastCons 1
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% Admixed American · 4/59,838 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000311% 5/1,606,178 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00668%	14,959
European (non-Finnish)	8.52e-05%	1,173,449

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.Pro440=
Coding: c.1320T>C
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs758200534
Type: single nucleotide variant
Location: chr5:87353223 (GRCh38)

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

Disease context

capillary malformation-arteriovenous malformation syndrome — 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-pro440 (accessed [today's date]).

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