Is RASA1 p.Ala66= (c.198T>C) pathogenic?

RASA1 p.Ala66= (c.198T>C) is classified Likely benign in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). Very rare (popmax 0.00221%, sas); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Ala66= (c.198T>C)?

RASA1 p.Ala66= (c.198T>C) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ala66= (c.198T>C) in the general population?

RASA1 p.Ala66= (c.198T>C) is very rare (popmax 0.00221%, sas) (gnomAD).

RASA1 p.Ala66=

c.198T>C · VCV3705290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Conditions

capillary malformation-arteriovenous malformation syndrome

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 -0.72	GERP -0.4
Overall
CADD	9.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,656 alleles

Filtering AF 0.000366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,458,990 alleles · very rare

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.Ala66=
Coding: c.198T>C
MANE Select: NM_002890
Type: single nucleotide variant
Location: chr5:87268649 (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

capillary malformation-arteriovenous malformation syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RASA1 p.Ala115Gly Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala115Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala125Gly Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala29Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala32Val Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala40Ser Uncertain significance ★★ ⚠ same condition
RASA1 p.Ala40Thr 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-ala66 (accessed [today's date]).

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