Is ARHGAP39 p.Arg963= (c.2889G>A) pathogenic?

ARHGAP39 p.Arg963= (c.2889G>A) is classified Likely benign in ARHGAP39 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). Very rare (popmax 0.00893%, amr).

How common is ARHGAP39 p.Arg963= (c.2889G>A) in the general population?

ARHGAP39 p.Arg963= (c.2889G>A) is very rare (popmax 0.00893%, amr) (gnomAD).

ARHGAP39 p.Arg963=

c.2889G>A · VCV4136969

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00893%, amr)

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 0.59	GERP -1.5, phastCons 1
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% Admixed American · 5/56,008 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00219%

Overall 0.000349% 5/1,433,690 alleles · very rare

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: ARHGAP39
Protein: p.Arg963=
Coding: c.2889G>A
MANE Select: NM_025251
Type: single nucleotide variant
Location: chr8:144532396 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.42
Residue 963: the rho-gap domain

Full ARHGAP39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP39 p.Arg933Cys Uncertain significance ★★ ⚠ same type
ARHGAP39 p.Ala227= Benign ★★ same type
ARHGAP39 p.Thr818= Benign ★★ same type
ARHGAP39 p.Ala1033Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala1056Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala120Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala322Asp Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala322Thr 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/arhgap39-p-arg963 (accessed [today's date]).

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