Is RASA1 p.Pro145= (c.435T>A) pathogenic?

RASA1 p.Pro145= (c.435T>A) is classified Likely benign in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-30). Very rare (popmax 0.0011%, nfe); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro145= (c.435T>A)?

RASA1 p.Pro145= (c.435T>A) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro145= (c.435T>A) in the general population?

RASA1 p.Pro145= (c.435T>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

RASA1 p.Pro145=

c.435T>A · rs754019936 · VCV1740006

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

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 -0.39	GERP -2.2, phastCons 0.001
Overall
CADD	7.655	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,948 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000806% 13/1,613,838 alleles · very rare exomes 13/1,461,636 · genomes 0/152,202 · 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.Pro145=
Coding: c.435T>A
MANE Select: NM_002890
dbSNP: rs754019936
Type: single nucleotide variant
Location: chr5:87268886 (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.Pro145His Uncertain significance ★★ ⚠ same residue
RASA1 p.Pro145Arg Uncertain significance ★ ⚠ same residue
RASA1 p.Pro145Ser Uncertain significance ★ ⚠ same residue
RASA1 p.Pro145fs Pathogenic ★ same residue
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

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-pro145 (accessed [today's date]).

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