Is ARHGAP44 p.Glu448Asp (c.1344G>C) pathogenic?

ARHGAP44 p.Glu448Asp (c.1344G>C) is classified Uncertain significance in ARHGAP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-17). AlphaMissense: likely benign (0.0664); Ultra-rare (popmax 0.0934%, sas).

How common is ARHGAP44 p.Glu448Asp (c.1344G>C) in the general population?

ARHGAP44 p.Glu448Asp (c.1344G>C) is ultra-rare (popmax 0.0934%, sas) (gnomAD).

What do computational predictors say about ARHGAP44 p.Glu448Asp (c.1344G>C)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

ARHGAP44 p.Glu448Asp

c.1344G>C · rs528206366 · VCV2407707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0934%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 184 kb · p 5.2e-15 · regional, not allelic
Overall
CADD	14.69	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0934% South Asian · 85/91,032 alleles

Filtering AF 0.0773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0714%

Overall 0.00558% 90/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0934%	1,071
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000254%	393,273

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.Glu448Asp
Coding: c.1344G>C
MANE Select: NM_014859
dbSNP: rs528206366
Type: single nucleotide variant
Location: chr17:12958718 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.39

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-glu448asp (accessed [today's date]).

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