Is ARHGAP39 p.Arg415Gln (c.1244G>A) pathogenic?

ARHGAP39 p.Arg415Gln (c.1244G>A) is classified Uncertain significance in ARHGAP39 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.146); Very rare (popmax 0.00114%, sas).

How common is ARHGAP39 p.Arg415Gln (c.1244G>A) in the general population?

ARHGAP39 p.Arg415Gln (c.1244G>A) is very rare (popmax 0.00114%, sas) (gnomAD).

What do computational predictors say about ARHGAP39 p.Arg415Gln (c.1244G>A)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

ARHGAP39 p.Arg415Gln

c.1244G>A · rs750579993 · VCV3128822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.64	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 4.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00114% South Asian · 1/87,998 alleles

Overall 0.000139% 2/1,433,796 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00114%	87,998
European (non-Finnish)	8.57e-05%	1,167,080

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.Arg415Gln
Coding: c.1244G>A
MANE Select: NM_025251
dbSNP: rs750579993
Type: single nucleotide variant
Location: chr8:144547842 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.42
Residue 415: the 'disordered' region

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-arg415gln (accessed [today's date]).

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