Is RASA1 p.Ile232Val (c.694A>G) pathogenic?

RASA1 p.Ile232Val (c.694A>G) is classified Conflicting classifications of pathogenicity in RASA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-04). AlphaMissense: ambiguous (0.3491); Very rare (popmax 0.00224%, eas); Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Ile232Val (c.694A>G)?

RASA1 p.Ile232Val (c.694A>G) is associated with Cardiovascular phenotype, capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ile232Val (c.694A>G) in the general population?

RASA1 p.Ile232Val (c.694A>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about RASA1 p.Ile232Val (c.694A>G)?

AlphaMissense predicts ambiguous (score 0.3491) — an in-silico prediction, not a clinical call.

RASA1 p.Ile232Val

c.694A>G · rs201997632 · VCV2994520

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3491	ambiguous
REVEL	0.28	benign-leaning
SaProt	LLR -7.57	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 5e-15 · regional, not allelic
Overall
CADD	24.2	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 0.00224% East Asian · 1/44,620 alleles

Overall 0.000125% 2/1,606,366 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,620
European (non-Finnish)	8.52e-05%	1,173,564

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.Ile232Val
Coding: c.694A>G
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs201997632
Type: single nucleotide variant
Location: chr5:87332508 (GRCh38)

Full RASA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: capillary malformation-arteriovenous malformation syndrome

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-ile232val (accessed [today's date]).

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