Is RASA2 p.Trp137Arg (c.409T>C) pathogenic?

RASA2 p.Trp137Arg (c.409T>C) is classified Uncertain significance in RASA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-19). Absent from gnomAD v4.1; Associated with RASA2-related disorder.

What condition is associated with RASA2 p.Trp137Arg (c.409T>C)?

RASA2 p.Trp137Arg (c.409T>C) is associated with RASA2-related disorder (ClinVar).

How common is RASA2 p.Trp137Arg (c.409T>C) in the general population?

RASA2 p.Trp137Arg (c.409T>C) is absent from gnomAD v4.1 (gnomAD).

RASA2 p.Trp137Arg

c.409T>C · rs2478525003 · VCV2637155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

RASA2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.863	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 121 kb · p 0.039 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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: RASA2
Protein: p.Trp137Arg
Coding: c.409T>C
MANE Select: NM_006506
dbSNP: rs2478525003
Type: single nucleotide variant
Location: chr3:141529761 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63
Residue 137: the c2 1 domain

Full RASA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RASA2-related disorder

Similar variants

RASA2 p.Ser666Arg Uncertain significance ★★ same condition
RASA2 p.Val660Met Uncertain significance ★★ same condition
RASA2 c.611+1G>T Uncertain significance ★ same condition
RASA2 p.Ala380Thr Uncertain significance ★ same condition
RASA2 p.Asn146Lys Uncertain significance ★ same condition
RASA2 p.Asn277Lys Conflicting classifications of pathogenicity ★ same condition
RASA2 p.Val517Leu Conflicting classifications of pathogenicity ★ same condition
RASA2 p.Val654Ile Conflicting classifications of pathogenicity ★ 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/rasa2-p-trp137arg (accessed [today's date]).

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