Is RASA1 p.Val227Phe (c.679G>T) pathogenic?

RASA1 p.Val227Phe (c.679G>T) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-11). AlphaMissense: likely pathogenic (0.9253); Absent from gnomAD v4.1; Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Val227Phe (c.679G>T)?

RASA1 p.Val227Phe (c.679G>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Val227Phe (c.679G>T) in the general population?

RASA1 p.Val227Phe (c.679G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASA1 p.Val227Phe (c.679G>T)?

AlphaMissense predicts likely pathogenic (score 0.9253) — an in-silico prediction, not a clinical call.

RASA1 p.Val227Phe

c.679G>T · rs2531187741 · VCV2918070

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9253 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary malformation-arteriovenous malformation syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9253	likely pathogenic
REVEL	0.797	moderately pathogenic-leaning
SaProt	LLR -9.08	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 5e-15 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RASA1
Protein: p.Val227Phe
Coding: c.679G>T
MANE Select: NM_002890
dbSNP: rs2531187741
Type: single nucleotide variant
Location: chr5:87331487 (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-val227phe (accessed [today's date]).

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