Is RASA2 p.Arg511His (c.1532G>A) pathogenic?

RASA2 p.Arg511His (c.1532G>A) is classified Uncertain significance in RASA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-24). Very rare (popmax 0.00268%, afr).

How common is RASA2 p.Arg511His (c.1532G>A) in the general population?

RASA2 p.Arg511His (c.1532G>A) is very rare (popmax 0.00268%, afr) (gnomAD).

RASA2 p.Arg511His

c.1532G>A · VCV4964534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.774	moderately pathogenic-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 121 kb · p 0.039 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,620 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.0013% 21/1,610,846 alleles · very rare exomes 20/1,459,264 · genomes 1/151,582 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,550
African / African-Americangrpmax	0.00268%	37,310
East Asian	0.00224%	44,598
South Asian	0.0022%	45,394
European (non-Finnish)	0.00127%	78,568

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg511His
Coding: c.1532G>A
MANE Select: NM_006506
Type: single nucleotide variant
Location: chr3:141577048 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63
Residue 511: the ras-gap domain

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

Similar variants

RASA2 p.Arg511Cys 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-arg511his (accessed [today's date]).

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