Is RASA1 p.Ala80Val (c.239C>T) pathogenic?

RASA1 p.Ala80Val (c.239C>T) is classified Uncertain significance in RASA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-14). AlphaMissense: likely benign (0.0788); Very rare (popmax 0.000424%, nfe); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Ala80Val (c.239C>T)?

RASA1 p.Ala80Val (c.239C>T) is associated with capillary malformation-arteriovenous malformation syndrome, basal cell carcinoma, susceptibility to, 1, capillary malformation-arteriovenous malformation 1 (ClinVar).

How common is RASA1 p.Ala80Val (c.239C>T) in the general population?

RASA1 p.Ala80Val (c.239C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about RASA1 p.Ala80Val (c.239C>T)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

RASA1 p.Ala80Val

c.239C>T · rs764720303 · VCV1000681

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.26	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 -0.4	GERP -2.2
Regional constraint	o/e 1.18	unconstrained · MANE · 63 kb · p 0.0025 · regional, not allelic
Overall
CADD	3.696	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,178,894 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000343% 5/1,458,850 alleles · very rare

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.Ala80Val
Coding: c.239C>T
MANE Select: NM_002890
dbSNP: rs764720303
Type: single nucleotide variant
Location: chr5:87268690 (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

Also linked: basal cell carcinoma, susceptibility to, 1 capillary malformation-arteriovenous malformation 1

Similar variants

RASA1 p.Ala80Thr Uncertain significance ★ ⚠ same residue
RASA1 p.Ala80= Likely benign ★ 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
RASA1 p.Ala32Val 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-ala80val (accessed [today's date]).

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