Is ARHGAP29 p.Pro681= (c.2043A>G) pathogenic?

ARHGAP29 p.Pro681= (c.2043A>G) is classified Likely benign in ARHGAP29 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-05). Very rare (popmax 0.000509%, nfe); Associated with ARHGAP29-related disorder.

What condition is associated with ARHGAP29 p.Pro681= (c.2043A>G)?

ARHGAP29 p.Pro681= (c.2043A>G) is associated with ARHGAP29-related disorder (ClinVar).

How common is ARHGAP29 p.Pro681= (c.2043A>G) in the general population?

ARHGAP29 p.Pro681= (c.2043A>G) is very rare (popmax 0.000509%, nfe) (gnomAD).

ARHGAP29 p.Pro681=

c.2043A>G · rs1451917679 · VCV3031254

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

ARHGAP29-related disorder

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 1.1	GERP 0.53, phastCons 1
Overall
CADD	8.707	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,802 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,572 alleles · very rare exomes 3/1,461,328 · genomes 3/152,244 · joint denominator

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: ARHGAP29
Protein: p.Pro681=
Coding: c.2043A>G
MANE Select: NM_004815
dbSNP: rs1451917679
Type: single nucleotide variant
Location: chr1:94184938 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.41
Residue 681: the rho-gap domain

Full ARHGAP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARHGAP29-related disorder

Similar variants

ARHGAP29 c.1682-12A>G Likely pathogenic ★ same condition
ARHGAP29 p.Ser552Pro Pathogenic ★ ⚠ same condition
ARHGAP29 c.2481-1G>A Conflicting classifications of pathogenicity ★ ⚠ same condition
ARHGAP29 c.2796+5G>C Uncertain significance ★ same condition
ARHGAP29 p.Ile410Ser Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Arg1024Gly Uncertain significance ⚠ same condition
ARHGAP29 p.Arg415Gln Uncertain significance ⚠ same condition
ARHGAP29 c.1144-9T>A Likely benign same condition

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/arhgap29-p-pro681 (accessed [today's date]).

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