Is RASA1 p.Phe535= (c.1605T>C) pathogenic?

RASA1 p.Phe535= (c.1605T>C) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00334%, amr); Associated with Cardiovascular phenotype.

What condition is associated with RASA1 p.Phe535= (c.1605T>C)?

RASA1 p.Phe535= (c.1605T>C) is associated with Cardiovascular phenotype, capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Phe535= (c.1605T>C) in the general population?

RASA1 p.Phe535= (c.1605T>C) is very rare (popmax 0.00334%, amr) (gnomAD).

RASA1 p.Phe535=

c.1605T>C · rs1459643901 · VCV766240

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Cardiovascular phenotype

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 0.34	GERP -3.8, phastCons 1
Overall
CADD	7.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,944 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,611,220 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,972
European (non-Finnish)	0.000425%	235,569

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.Phe535=
Coding: c.1605T>C
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs1459643901
Type: single nucleotide variant
Location: chr5:87363499 (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-phe535 (accessed [today's date]).

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