Is RASA2 p.Ile353= (c.1059A>C) pathogenic?

RASA2 p.Ile353= (c.1059A>C) is classified Likely benign in RASA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-19). Very rare (popmax 0.00017%, nfe).

How common is RASA2 p.Ile353= (c.1059A>C) in the general population?

RASA2 p.Ile353= (c.1059A>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

RASA2 p.Ile353=

c.1059A>C · rs2478713278 · VCV2026499

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.4, phastCons 1
Overall
CADD	7.813	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,846 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,804 alleles · very rare exomes 2/1,461,506 · genomes 0/152,298 · joint denominator

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: RASA2
Protein: p.Ile353=
Coding: c.1059A>C
MANE Select: NM_006506
dbSNP: rs2478713278
Type: single nucleotide variant
Location: chr3:141571444 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63

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

Similar variants

RASA2 p.Ile353Leu Uncertain significance ★ same residue
RASA2 c.612-3C>T Uncertain significance ★★ same type
RASA2 p.Ala360Gly Uncertain significance ★★ same type
RASA2 p.Ala489Thr Uncertain significance ★★ same type
RASA2 p.Ala503Ser Uncertain significance ★★ same type
RASA2 p.Ala742Val Uncertain significance ★★ same type
RASA2 p.Arg117His Uncertain significance ★★ same type
RASA2 p.Arg310Gln Uncertain significance ★★ same type

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-ile353 (accessed [today's date]).

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