Is RASA2 p.Leu735= (c.2205C>T) pathogenic?

RASA2 p.Leu735= (c.2205C>T) is classified Likely benign in RASA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-28). Very rare (popmax 0.00223%, eas).

How common is RASA2 p.Leu735= (c.2205C>T) in the general population?

RASA2 p.Leu735= (c.2205C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

RASA2 p.Leu735=

c.2205C>T · rs1029424231 · VCV984495

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -8.5	GERP -3.7
Overall
CADD	0.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000992% 16/1,613,608 alleles · very rare exomes 16/1,461,288 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
European (non-Finnish)	0.00127%	78,641

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.Leu735=
Coding: c.2205C>T
MANE Select: NM_006506
dbSNP: rs1029424231
Type: single nucleotide variant
Location: chr3:141608677 (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.Leu735Phe Uncertain significance ★ same residue
RASA2 p.Leu735Val 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

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-leu735 (accessed [today's date]).

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