Is ARHGAP27 p.Val9Met (c.25G>A) pathogenic?

ARHGAP27 p.Val9Met (c.25G>A) is classified Uncertain significance in ARHGAP27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). AlphaMissense: ambiguous (0.5175); Very rare (popmax 0.0094%, afr).

How common is ARHGAP27 p.Val9Met (c.25G>A) in the general population?

ARHGAP27 p.Val9Met (c.25G>A) is very rare (popmax 0.0094%, afr) (gnomAD).

What do computational predictors say about ARHGAP27 p.Val9Met (c.25G>A)?

AlphaMissense predicts ambiguous (score 0.5175) — an in-silico prediction, not a clinical call.

ARHGAP27 p.Val9Met

c.25G>A · rs546150279 · VCV3128689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5175 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0094%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5175	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.2, phastCons 1
Overall
CADD	26.3	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 0.0094% African / African-American · 7/74,494 alleles

Filtering AF 0.00439% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.000887% 14/1,578,094 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0094%	10,642
East Asian	0.00229%	43,656
Admixed American	0.00175%	57,162
Remaining individualsnot grpmax-eligible	0.00163%	61,518
European (non-Finnish)	0.000342%	292,629

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.Val9Met
Coding: c.25G>A
MANE Select: NM_001282290
dbSNP: rs546150279
Type: single nucleotide variant
Location: chr17:45430255 (GRCh38)
Gene constraint: LOEUF 0.709 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.53 · 1 PDB
Residue 9: the sh3 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-val9met (accessed [today's date]).

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