Is ARHGAP39 p.Pro310Thr (c.928C>A) pathogenic?

ARHGAP39 p.Pro310Thr (c.928C>A) is classified Uncertain significance in ARHGAP39 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-05). AlphaMissense: ambiguous (0.4592); Very rare (popmax 0.00902%, eas).

How common is ARHGAP39 p.Pro310Thr (c.928C>A) in the general population?

ARHGAP39 p.Pro310Thr (c.928C>A) is very rare (popmax 0.00902%, eas) (gnomAD).

What do computational predictors say about ARHGAP39 p.Pro310Thr (c.928C>A)?

AlphaMissense predicts ambiguous (score 0.4592) — an in-silico prediction, not a clinical call.

ARHGAP39 p.Pro310Thr

c.928C>A · rs778326683 · VCV2592347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4592 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00902%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4592	ambiguous
REVEL	0.25	benign-leaning
SaProt	LLR -7.50	tolerated
⇒ 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
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 35 kb · p 0.0019 · regional, not allelic
Overall
CADD	25.2	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 0.00902% East Asian · 4/44,346 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00182%

Overall 0.000422% 6/1,422,472 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00902%	11,086
African / African-American	0.00135%	73,878
South Asian	0.00117%	85,612

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.Pro310Thr
Coding: c.928C>A
MANE Select: NM_025251
dbSNP: rs778326683
Type: single nucleotide variant
Location: chr8:144548158 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.42
Residue 310: the 'disordered' region

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

Similar variants

ARHGAP39 p.Pro310Arg Uncertain significance ★ ⚠ same residue
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

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-pro310thr (accessed [today's date]).

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