Is ARHGAP39 p.Glu50Asp (c.150G>T) pathogenic?

ARHGAP39 p.Glu50Asp (c.150G>T) is classified Uncertain significance in ARHGAP39 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.8386); Very rare (popmax 0.000174%, nfe).

How common is ARHGAP39 p.Glu50Asp (c.150G>T) in the general population?

ARHGAP39 p.Glu50Asp (c.150G>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about ARHGAP39 p.Glu50Asp (c.150G>T)?

AlphaMissense predicts likely pathogenic (score 0.8386) — an in-silico prediction, not a clinical call.

ARHGAP39 p.Glu50Asp

c.150G>T · VCV3891277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8386 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8386	likely pathogenic
REVEL	0.191	benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.25 · regional, not allelic
Overall
CADD	24.7	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 0.000174% European (non-Finnish) · 2/1,151,014 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000128% 2/1,556,854 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: ARHGAP39
Protein: p.Glu50Asp
Coding: c.150G>T
MANE Select: NM_025251
Type: single nucleotide variant
Location: chr8:144581208 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.42
Residue 50: the ww 1 domain

Full ARHGAP39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP39 p.Arg933Cys Uncertain significance ★★ ⚠ same type
ARHGAP39 p.Ala227= Benign ★★ same type
ARHGAP39 p.Thr818= Benign ★★ same type
ARHGAP39 p.Ala1033Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala1056Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala120Val Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala322Asp Uncertain significance ★ ⚠ same type
ARHGAP39 p.Ala322Thr 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/arhgap39-p-glu50asp (accessed [today's date]).

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