Is RASA1 p.Ser203Arg (c.607A>C) pathogenic?

RASA1 p.Ser203Arg (c.607A>C) is classified Uncertain significance in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-28). AlphaMissense: likely pathogenic (0.9828); Very rare (popmax 0.000509%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Ser203Arg (c.607A>C)?

RASA1 p.Ser203Arg (c.607A>C) is associated with Cardiovascular phenotype, capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ser203Arg (c.607A>C) in the general population?

RASA1 p.Ser203Arg (c.607A>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about RASA1 p.Ser203Arg (c.607A>C)?

AlphaMissense predicts likely pathogenic (score 0.9828) — an in-silico prediction, not a clinical call.

RASA1 p.Ser203Arg

c.607A>C · rs2531187416 · VCV1717317

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

⚠ 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	0.9828	likely pathogenic
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -15.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 63 kb · p 0.0025 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,692 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,792 alleles · very rare exomes 6/1,461,446 · genomes 0/152,346 · joint denominator

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.Ser203Arg
Coding: c.607A>C
MANE Select: NM_002890
dbSNP: rs2531187416
Type: single nucleotide variant
Location: chr5:87331415 (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-ser203arg (accessed [today's date]).

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