Is ARHGAP31 p.Gly49fs (c.146del) pathogenic?

ARHGAP31 p.Gly49fs (c.146del) is classified Uncertain significance in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). Very rare (popmax 0.00167%, amr).

How common is ARHGAP31 p.Gly49fs (c.146del) in the general population?

ARHGAP31 p.Gly49fs (c.146del) is very rare (popmax 0.00167%, amr) (gnomAD).

ARHGAP31 p.Gly49fs

c.146del · VCV3381449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.3	GERP -5.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 6.84e-05% 1/1,461,806 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: ARHGAP31
Protein: p.Gly49fs
Coding: c.146del
MANE Select: NM_020754
Type: Deletion
Location: chr3:119365360 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 49: the rho-gap domain

Full ARHGAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP31 p.Gly49Ser Uncertain significance ★ ⚠ same residue
ARHGAP31 p.Gly49= Likely benign ★ same residue
ARHGAP31 c.100+19del Benign/Likely benign ★★ same type
ARHGAP31 p.Pro567fs Likely pathogenic ★ same type
ARHGAP31 c.882-11_882-5del Uncertain significance ★ same type
ARHGAP31 p.Cys1424fs Uncertain significance ★ same type
ARHGAP31 p.Leu1050_His1052del Conflicting classifications of pathogenicity ★ same type
ARHGAP31 p.Leu602del 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/arhgap31-p-gly49fs (accessed [today's date]).

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