Is RASA1 p.Arg285Ter (c.853C>T) pathogenic?

RASA1 p.Arg285Ter (c.853C>T) is classified Pathogenic in RASA1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-25). Very rare (popmax 8.48e-05%, nfe); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Arg285Ter (c.853C>T)?

RASA1 p.Arg285Ter (c.853C>T) is associated with capillary malformation-arteriovenous malformation syndrome, capillary malformation-arteriovenous malformation 1, vascular malformation (ClinVar).

How common is RASA1 p.Arg285Ter (c.853C>T) in the general population?

RASA1 p.Arg285Ter (c.853C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

RASA1 p.Arg285Ter

c.853C>T · rs137853218 · VCV16001

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.45	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,240 alleles

Overall 6.85e-05% 1/1,460,742 alleles · very rare

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.Arg285Ter
Coding: c.853C>T
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs137853218
Type: single nucleotide variant
Location: chr5:87333291 (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

Also linked: capillary malformation-arteriovenous malformation 1 vascular malformation

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-arg285ter (accessed [today's date]).

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