Is ARHGAP27 p.Ala522Asp (c.1565C>A) pathogenic?

ARHGAP27 p.Ala522Asp (c.1565C>A) is classified Uncertain significance in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: ambiguous (0.4447); Absent from gnomAD v4.1.

How common is ARHGAP27 p.Ala522Asp (c.1565C>A) in the general population?

ARHGAP27 p.Ala522Asp (c.1565C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP27 p.Ala522Asp (c.1565C>A)?

AlphaMissense predicts ambiguous (score 0.4447) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Ala522Asp

c.1565C>A · VCV4135163

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4447 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4447	ambiguous
REVEL	0.417	indeterminate
SaProt	LLR -12.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 0.94, phastCons 1
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP27
Protein: p.Ala522Asp
Coding: c.1565C>A
MANE Select: NM_001282290
Type: single nucleotide variant
Location: chr17:45403692 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB
Residue 522: a β-strand; the ph domain

Full ARHGAP27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP27 c.657+107G>T Uncertain significance ★ same type
ARHGAP27 c.657+130G>A Uncertain significance ★ same type
ARHGAP27 c.657+26G>A Uncertain significance ★ same type
ARHGAP27 c.657+31G>A Uncertain significance ★ same type
ARHGAP27 c.657+34T>A Uncertain significance ★ same type
ARHGAP27 c.657+38G>A Uncertain significance ★ same type
ARHGAP27 c.657+49C>T Uncertain significance ★ same type
ARHGAP27 c.657+53C>T 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/arhgap27-p-ala522asp (accessed [today's date]).

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