Is ARHGAP44 p.Pro687Gln (c.2060C>A) pathogenic?

ARHGAP44 p.Pro687Gln (c.2060C>A) is classified Uncertain significance in ARHGAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.4269); Very rare (popmax 0.0028%, nfe).

How common is ARHGAP44 p.Pro687Gln (c.2060C>A) in the general population?

ARHGAP44 p.Pro687Gln (c.2060C>A) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about ARHGAP44 p.Pro687Gln (c.2060C>A)?

AlphaMissense predicts ambiguous (score 0.4269) — an in-silico prediction, not a clinical call.

ARHGAP44 p.Pro687Gln

c.2060C>A · rs779794969 · VCV2596300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4269	ambiguous
REVEL	0.35	indeterminate
SaProt	LLR -8.00	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.47 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0028% European (non-Finnish) · 33/1,179,628 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00211% 34/1,612,818 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,746
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Pro687Gln
Coding: c.2060C>A
MANE Select: NM_014859
dbSNP: rs779794969
Type: single nucleotide variant
Location: chr17:12984651 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.39
Residue 687: the 'disordered' region

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

Similar variants

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
ARHGAP44 p.Ala366Thr Uncertain significance ★ ⚠ same type
ARHGAP44 p.Ala526Val 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-pro687gln (accessed [today's date]).

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