Is RASA1 p.Pro614= (c.1842A>G) pathogenic?

RASA1 p.Pro614= (c.1842A>G) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). Very rare (popmax 0.00269%, afr); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro614= (c.1842A>G)?

RASA1 p.Pro614= (c.1842A>G) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro614= (c.1842A>G) in the general population?

RASA1 p.Pro614= (c.1842A>G) is very rare (popmax 0.00269%, afr) (gnomAD).

RASA1 p.Pro614=

c.1842A>G · rs376280581 · VCV1532738

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP 0.062	GERP -5.6, phastCons 0.044
Overall
CADD	6.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00269% African / African-American · 2/74,314 alleles

Filtering AF 0.000447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000626% 10/1,596,402 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0065%	15,388
African / African-Americangrpmax	0.00269%	37,157
Admixed American	0.00168%	59,472
European (non-Finnish)	0.000256%	389,912

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro614=
Coding: c.1842A>G
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs376280581
Type: single nucleotide variant
Location: chr5:87374228 (GRCh38)

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

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-pro614 (accessed [today's date]).

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