Is RASA1 p.Ser247Phe (c.740C>T) pathogenic?

RASA1 p.Ser247Phe (c.740C>T) is classified Uncertain significance in RASA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.3513); Absent from gnomAD v4.1; Associated with capillary malformation-arteriovenous malformation syndrome.

What condition is associated with RASA1 p.Ser247Phe (c.740C>T)?

RASA1 p.Ser247Phe (c.740C>T) is associated with capillary malformation-arteriovenous malformation syndrome (ClinVar).

How common is RASA1 p.Ser247Phe (c.740C>T) in the general population?

RASA1 p.Ser247Phe (c.740C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASA1 p.Ser247Phe (c.740C>T)?

AlphaMissense predicts ambiguous (score 0.3513) — an in-silico prediction, not a clinical call.

RASA1 p.Ser247Phe

c.740C>T · VCV4721993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3513 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

capillary malformation-arteriovenous malformation syndrome

Computational evidence

Protein change
AlphaMissense	0.3513	ambiguous
REVEL	0.239	benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 22 kb · p 5e-15 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RASA1
Protein: p.Ser247Phe
Coding: c.740C>T
MANE Select: NM_001239 · reported on NM_002890
Type: single nucleotide variant
Location: chr5:87332554 (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-ser247phe (accessed [today's date]).

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