Is RASA1 p.Ser219= (c.657A>G) pathogenic?

RASA1 p.Ser219= (c.657A>G) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-01). Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Ser219= (c.657A>G)?

RASA1 p.Ser219= (c.657A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is RASA1 p.Ser219= (c.657A>G) in the general population?

RASA1 p.Ser219= (c.657A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

RASA1 p.Ser219=

c.657A>G · rs1241440895 · VCV1754274

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

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

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.62	GERP -5, phastCons 0.93
Overall
CADD	8.735	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,858 alleles

Overall 6.2e-05% 1/1,613,752 alleles · very rare exomes 0/1,461,604 · genomes 1/152,148 · 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.Ser219=
Coding: c.657A>G
MANE Select: NM_002890
dbSNP: rs1241440895
Type: single nucleotide variant
Location: chr5:87331465 (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

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-ser219 (accessed [today's date]).

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