Is ARHGAP44 p.Pro683= (c.2049G>C) pathogenic?

ARHGAP44 p.Pro683= (c.2049G>C) is classified Likely benign in ARHGAP44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-07). Rare (popmax 0.8%, nfe); Associated with ARHGAP44-related disorder.

What condition is associated with ARHGAP44 p.Pro683= (c.2049G>C)?

ARHGAP44 p.Pro683= (c.2049G>C) is associated with ARHGAP44-related disorder (ClinVar).

How common is ARHGAP44 p.Pro683= (c.2049G>C) in the general population?

ARHGAP44 p.Pro683= (c.2049G>C) is rare (popmax 0.8%, nfe) (gnomAD).

ARHGAP44 p.Pro683=

c.2049G>C · rs1490592862 · VCV3033390

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.8%, nfe)

Conditions

ARHGAP44-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 -2.4	GERP -3.8
Overall
CADD	0.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.8% European (non-Finnish) · 3,641/455,156 alleles

Filtering AF 0.778% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.769%

Overall 0.609% 4,523/742,450 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.8%	125
East Asian	0.77%	130
Remaining individualsnot grpmax-eligible	0.753%	133
Ashkenazi Jewishnot grpmax-eligible	0.446%	224
Finnishnot grpmax-eligible	0.352%	284
Middle Eastern	0.338%	296
African / African-American	0.241%	416
South Asian	0.146%	683
Admixed American	0.131%	761

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: ARHGAP44
Protein: p.Pro683=
Coding: c.2049G>C
MANE Select: NM_014859
dbSNP: rs1490592862
Type: single nucleotide variant
Location: chr17:12984640 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.39
Residue 683: the 'disordered' region

Full ARHGAP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARHGAP44-related disorder

Similar variants

ARHGAP44 p.Pro683Leu Uncertain significance ★ ⚠ same residue
ARHGAP44 p.Asp481Gly Uncertain significance ⚠ same condition
ARHGAP44 p.Gln414= Benign ★★ same type
ARHGAP44 c.198+1G>A Uncertain significance ★ same type
ARHGAP44 p.Ala128Val Uncertain significance ★ ⚠ same type
ARHGAP44 p.Ala172Val Uncertain significance ★ ⚠ same type
ARHGAP44 p.Ala186Thr Uncertain significance ★ ⚠ same type
ARHGAP44 p.Ala304Val 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/arhgap44-p-pro683 (accessed [today's date]).

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