Is ARHGAP27 p.Pro364Ala (c.1090C>G) pathogenic?

ARHGAP27 p.Pro364Ala (c.1090C>G) is classified Uncertain significance in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: ambiguous (0.3564); Very rare (popmax 0.00672%, eas).

How common is ARHGAP27 p.Pro364Ala (c.1090C>G) in the general population?

ARHGAP27 p.Pro364Ala (c.1090C>G) is very rare (popmax 0.00672%, eas) (gnomAD).

What do computational predictors say about ARHGAP27 p.Pro364Ala (c.1090C>G)?

AlphaMissense predicts ambiguous (score 0.3564) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Pro364Ala

c.1090C>G · rs1401021719 · VCV3128694

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3564 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00672%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3564	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	22.4	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 0.00672% East Asian · 3/44,674 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000894%

Overall 0.000188% 3/1,595,432 alleles · very rare

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: ARHGAP27
Protein: p.Pro364Ala
Coding: c.1090C>G
MANE Select: NM_001282290
dbSNP: rs1401021719
Type: single nucleotide variant
Location: chr17:45405082 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB
Residue 364: the 'disordered' region

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-pro364ala (accessed [today's date]).

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