Is RASA1 p.Pro136fs (c.402del) pathogenic?

RASA1 p.Pro136fs (c.402del) is classified Pathogenic in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). Absent from gnomAD; Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro136fs (c.402del)?

RASA1 p.Pro136fs (c.402del) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro136fs (c.402del) in the general population?

RASA1 p.Pro136fs (c.402del) is absent from gnomAD (gnomAD).

RASA1 p.Pro136fs

c.402del · rs2531003398 · VCV2893369

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -1.5, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RASA1
Protein: p.Pro136fs
Coding: c.402del
MANE Select: NM_002890
dbSNP: rs2531003398
Type: Deletion
Location: chr5:87268850 (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.Pro136Arg Uncertain significance ★ ⚠ same residue
RASA1 p.Pro136Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RASA1 p.Glu5fs Pathogenic/Likely pathogenic ★★ same condition
RASA1 p.Ala58fs Pathogenic ★ same condition
RASA1 p.Ala78fs Pathogenic ★ same condition
RASA1 p.Gln180fs Pathogenic ★ same condition
RASA1 p.Ser27fs Pathogenic ★ same condition
RASA1 p.93AGVAGAA[1] 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-pro136fs (accessed [today's date]).

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