Sugi Variant
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ARHGAP8/p.Val17Met

ARHGAP8 p.Val17Met

c.49G>A · rs200833725 · VCV3128959

Uncertain significance Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5078 · ACMG-weighted
gnomAD v4.1
Rare
ultra-rare (popmax 0.0163%, nfe)
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense0.5078ambiguous
REVEL0.127moderately benign-leaning
SaProtLLR -9.45tolerated
⇒ 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
ConservationphyloP 5.7phastCons 1
Regional constrainto/e 1.62unconstrained · MANE · 76 kb · p 4.7e-50 · regional, not allelic
Overall
CADD24.8PHRED · 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 0.0163% European (non-Finnish) · 192/1,179,768 alleles
Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%
Overall 0.0195% 315/1,613,302 alleles · ultra-rare
Ancestry group Frequency 1 in
Ashkenazi Jewishnot grpmax-eligible 0.182% 548
Finnishnot grpmax-eligible 0.0501% 1,996
Remaining individualsnot grpmax-eligible 0.024% 4,163
European (non-Finnish)grpmax 0.0163% 6,145
South Asian 0.0154% 6,498
African / African-American 0.00667% 14,983
Admixed American 0.00334% 29,975
East Asian 0.00223% 44,890

Ashkenazi Jewish 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
ARHGAP8
Protein
p.Val17Met
Coding
c.49G>A
MANE Select
NM_181335
dbSNP
rs200833725
Type
single nucleotide variant
Location
chr22:44786576 (GRCh38)
Gene constraint
LOEUF 1.648 · pLI <0.01 (gnomAD)
Structure
AlphaFold pLDDT 76.51
Residue 17
the cral-trio domain
Full ARHGAP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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/arhgap8-p-val17met (accessed [today's date]).

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