Is RASA1 p.Ser215Phe (c.644C>T) pathogenic?

RASA1 p.Ser215Phe (c.644C>T) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely pathogenic (0.9802); Very rare (popmax 0.00133%, afr); Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Ser215Phe (c.644C>T)?

RASA1 p.Ser215Phe (c.644C>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ser215Phe (c.644C>T) in the general population?

RASA1 p.Ser215Phe (c.644C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RASA1 p.Ser215Phe (c.644C>T)?

AlphaMissense predicts likely pathogenic (score 0.9802) — an in-silico prediction, not a clinical call.

RASA1 p.Ser215Phe

c.644C>T · rs1399533599 · VCV1950096

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.9802	likely pathogenic
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 5e-15 · regional, not allelic
Overall
CADD	27.9	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 0.00133% African / African-American · 1/75,022 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000753% 11/1,461,600 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,022
European (non-Finnish)	0.000848%	117,983

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.Ser215Phe
Coding: c.644C>T
MANE Select: NM_001239 · reported on NM_002890
dbSNP: rs1399533599
Type: single nucleotide variant
Location: chr5:87331452 (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-ser215phe (accessed [today's date]).

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