Is RASA1 p.Pro13= (c.39G>T) pathogenic?

RASA1 p.Pro13= (c.39G>T) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-17). Very rare (popmax 0.00781%, amr); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro13= (c.39G>T)?

RASA1 p.Pro13= (c.39G>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro13= (c.39G>T) in the general population?

RASA1 p.Pro13= (c.39G>T) is very rare (popmax 0.00781%, amr) (gnomAD).

RASA1 p.Pro13=

c.39G>T · rs969604375 · VCV1656594

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00781%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.34, phastCons 1
Overall
CADD	13.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00781% Admixed American · 4/51,186 alleles

Filtering AF 0.00262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.000578% 9/1,557,948 alleles · very rare exomes 6/1,408,134 · genomes 3/149,814 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00781%	12,796
European (non-Finnish)	0.000434%	230,484

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.Pro13=
Coding: c.39G>T
MANE Select: NM_002890
dbSNP: rs969604375
Type: single nucleotide variant
Location: chr5:87268490 (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

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

Similar variants

RASA1 p.Pro13Ala Uncertain significance ★ ⚠ same residue
RASA1 p.Pro13Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
RASA1 p.Pro13Leu Uncertain significance ★ ⚠ same residue
RASA1 p.Ala115Gly Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala115Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala125Gly Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala29Val 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-pro13 (accessed [today's date]).

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