Is RASA2 p.Pro85= (c.255A>G) pathogenic?

RASA2 p.Pro85= (c.255A>G) is classified Likely benign in RASA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-05). Very rare (popmax 0.00415%, afr).

How common is RASA2 p.Pro85= (c.255A>G) in the general population?

RASA2 p.Pro85= (c.255A>G) is very rare (popmax 0.00415%, afr) (gnomAD).

RASA2 p.Pro85=

c.255A>G · rs768464571 · VCV992229

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00415%, afr)

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 -0.14	GERP -4.9, phastCons 0.001
Overall
CADD	8.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00415% African / African-American · 3/72,220 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00085%

Overall 0.00148% 23/1,552,784 alleles · very rare exomes 20/1,401,294 · genomes 3/151,490 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00415%	24,073
European (non-Finnish)	0.00165%	60,664
South Asian	0.00127%	78,750

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.Pro85=
Coding: c.255A>G
MANE Select: NM_006506
dbSNP: rs768464571
Type: single nucleotide variant
Location: chr3:141516331 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.63
Residue 85: the c2 1 domain

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

Similar variants

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
RASA2 p.Arg366Gln 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-pro85 (accessed [today's date]).

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