Is ARHGAP27 p.Glu686Asp (c.2058G>C) pathogenic?

ARHGAP27 p.Glu686Asp (c.2058G>C) is classified Likely benign in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1218); Absent from gnomAD v4.1.

How common is ARHGAP27 p.Glu686Asp (c.2058G>C) in the general population?

ARHGAP27 p.Glu686Asp (c.2058G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP27 p.Glu686Asp (c.2058G>C)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Glu686Asp

c.2058G>C · rs2509364744 · VCV3128686

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.51	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 -2.7	GERP -4.2
Overall
CADD	10.85	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.Glu686Asp
Coding: c.2058G>C
MANE Select: NM_001282290
dbSNP: rs2509364744
Type: single nucleotide variant
Location: chr17:45396684 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB

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-glu686asp (accessed [today's date]).

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