Is RASA1 p.Pro13Arg (c.38C>G) pathogenic?

RASA1 p.Pro13Arg (c.38C>G) is classified Conflicting classifications of pathogenicity in RASA1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.1606); Very rare (popmax 0.00953%, eas); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Pro13Arg (c.38C>G)?

RASA1 p.Pro13Arg (c.38C>G) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Pro13Arg (c.38C>G) in the general population?

RASA1 p.Pro13Arg (c.38C>G) is very rare (popmax 0.00953%, eas) (gnomAD).

What do computational predictors say about RASA1 p.Pro13Arg (c.38C>G)?

AlphaMissense predicts likely benign (score 0.1606) — an in-silico prediction, not a clinical call.

RASA1 p.Pro13Arg

c.38C>G · rs761910879 · VCV2907518

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00953%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.1606	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 63 kb · p 0.0025 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00953% East Asian · 4/41,990 alleles

Filtering AF 0.00322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000995% 14/1,407,462 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00953%	10,497
South Asian	0.00708%	14,122
Remaining individualsnot grpmax-eligible	0.00497%	20,105
European (non-Finnish)	8.68e-05%	1,151,613

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.Pro13Arg
Coding: c.38C>G
MANE Select: NM_002890
dbSNP: rs761910879
Type: single nucleotide variant
Location: chr5:87268489 (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.Pro13= Likely benign ★★ same residue
RASA1 p.Pro13Ala Uncertain significance ★ ⚠ same residue
RASA1 p.Pro13Leu Uncertain significance ★ ⚠ 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
RASA1 p.Ala29Val 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-pro13arg (accessed [today's date]).

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