Is RASA1 p.Phe548= (c.1644T>C) pathogenic?

RASA1 p.Phe548= (c.1644T>C) is classified Likely benign in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.00448%, eas); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Phe548= (c.1644T>C)?

RASA1 p.Phe548= (c.1644T>C) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Phe548= (c.1644T>C) in the general population?

RASA1 p.Phe548= (c.1644T>C) is very rare (popmax 0.00448%, eas) (gnomAD).

RASA1 p.Phe548=

c.1644T>C · rs749876769 · VCV464853

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

capillary malformation-arteriovenous malformation syndrome

⚠ 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 2.4	GERP -2.9, phastCons 1
Overall
CADD	8.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,654 alleles

Filtering AF 0.000742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000992% 16/1,612,192 alleles · very rare exomes 15/1,460,038 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,327
Finnishnot grpmax-eligible	0.00313%	31,985
African / African-American	0.00134%	74,882
European (non-Finnish)	0.000933%	107,169

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.Phe548=
Coding: c.1644T>C
MANE Select: NM_002890
dbSNP: rs749876769
Type: single nucleotide variant
Location: chr5:87369846 (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-phe548 (accessed [today's date]).

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