Is RASA1 p.Ala4= (c.12C>A) pathogenic?

RASA1 p.Ala4= (c.12C>A) is classified Likely benign in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). Very rare (popmax 8.73e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Ala4= (c.12C>A)?

RASA1 p.Ala4= (c.12C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is RASA1 p.Ala4= (c.12C>A) in the general population?

RASA1 p.Ala4= (c.12C>A) is very rare (popmax 8.73e-05%, nfe) (gnomAD).

RASA1 p.Ala4=

c.12C>A · rs745761730 · VCV1769340

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.73e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.94	GERP 0.37, phastCons 1
Overall
CADD	13.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.73e-05% European (non-Finnish) · 1/1,145,882 alleles

Overall 6.47e-05% 1/1,546,458 alleles · very rare exomes 1/1,396,574 · genomes 0/149,884 · 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.Ala4=
Coding: c.12C>A
MANE Select: NM_002890
dbSNP: rs745761730
Type: single nucleotide variant
Location: chr5:87268463 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 15 PDB

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

Similar variants

RASA1 p.Ala4Thr Uncertain significance ★ ⚠ same residue
RASA1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala32Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala96Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Gly133Asp Uncertain significance ★★ ⚠ same condition
RASA1 p.Gly151Arg Uncertain significance ★★ same condition
RASA1 p.Gly85Ala Uncertain significance ★★ ⚠ same condition
RASA1 p.Gly88Arg Uncertain significance ★★ ⚠ same condition

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-ala4 (accessed [today's date]).

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