Is ARHGAP27 p.Arg583Trp (c.1747C>T) pathogenic?

ARHGAP27 p.Arg583Trp (c.1747C>T) is classified Uncertain significance in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.1632); Very rare (popmax 0.00535%, afr).

How common is ARHGAP27 p.Arg583Trp (c.1747C>T) in the general population?

ARHGAP27 p.Arg583Trp (c.1747C>T) is very rare (popmax 0.00535%, afr) (gnomAD).

What do computational predictors say about ARHGAP27 p.Arg583Trp (c.1747C>T)?

AlphaMissense predicts likely benign (score 0.1632) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Arg583Trp

c.1747C>T · rs368752990 · VCV3128696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1632 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1632	likely benign
REVEL	0.631	indeterminate
SaProt	LLR -13.89	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.3	GERP 1.8, phastCons 1
Overall
CADD	32.0	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 0.00535% African / African-American · 4/74,792 alleles

Filtering AF 0.0031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.00369% 59/1,600,932 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00811%	12,331
African / African-Americangrpmax	0.00535%	18,698
European (non-Finnish)	0.00402%	24,900
East Asian	0.00224%	44,662
Admixed American	0.00168%	59,682
South Asian	0.00111%	90,116

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg583Trp
Coding: c.1747C>T
MANE Select: NM_001282290
dbSNP: rs368752990
Type: single nucleotide variant
Location: chr17:45398044 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB
Residue 583: 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
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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-arg583trp (accessed [today's date]).

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