Is RASA1 p.Ala29Ser (c.85G>T) pathogenic?

RASA1 p.Ala29Ser (c.85G>T) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-04). AlphaMissense: likely benign (0.0796); Very rare (popmax 0.00375%, nfe); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Ala29Ser (c.85G>T)?

RASA1 p.Ala29Ser (c.85G>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ala29Ser (c.85G>T) in the general population?

RASA1 p.Ala29Ser (c.85G>T) is very rare (popmax 0.00375%, nfe) (gnomAD).

What do computational predictors say about RASA1 p.Ala29Ser (c.85G>T)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

RASA1 p.Ala29Ser

c.85G>T · rs777487947 · VCV2144140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00375%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.37	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 0.22	GERP -0.97
Regional constraint	o/e 1.18	unconstrained · MANE · 63 kb · p 0.0025 · regional, not allelic
Overall
CADD	5.504	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 0.00375% European (non-Finnish) · 44/1,172,780 alleles

Filtering AF 0.00284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00253%

Overall 0.00326% 47/1,443,856 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00375%	26,654
Admixed American	0.00177%	56,640
Remaining individualsnot grpmax-eligible	0.00162%	61,762
South Asian	0.00113%	88,248

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.Ala29Ser
Coding: c.85G>T
MANE Select: NM_002890
dbSNP: rs777487947
Type: single nucleotide variant
Location: chr5:87268536 (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.Ala29Val Uncertain significance ★★ ⚠ same residue
RASA1 p.Ala29Pro Uncertain significance ★ ⚠ same residue
RASA1 p.Ala29Thr Uncertain significance ★ ⚠ same residue
RASA1 p.Ala29= 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

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-ala29ser (accessed [today's date]).

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