Is RASA1 p.Arg464Cys (c.1390C>T) pathogenic?

RASA1 p.Arg464Cys (c.1390C>T) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-17). AlphaMissense: likely pathogenic (0.8124); Very rare (popmax 8.59e-05%, nfe); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Arg464Cys (c.1390C>T)?

RASA1 p.Arg464Cys (c.1390C>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Arg464Cys (c.1390C>T) in the general population?

RASA1 p.Arg464Cys (c.1390C>T) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

What do computational predictors say about RASA1 p.Arg464Cys (c.1390C>T)?

AlphaMissense predicts likely pathogenic (score 0.8124) — an in-silico prediction, not a clinical call.

RASA1 p.Arg464Cys

c.1390C>T · rs1760197131 · VCV1035381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.8124	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -9.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.59e-05% European (non-Finnish) · 1/1,164,006 alleles

Overall 6.92e-05% 1/1,444,110 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.Arg464Cys
Coding: c.1390C>T
MANE Select: NM_002890
dbSNP: rs1760197131
Type: single nucleotide variant
Location: chr5:87362608 (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-arg464cys (accessed [today's date]).

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