Is ARHGAP31 p.Pro787Ala (c.2359C>G) pathogenic?

ARHGAP31 p.Pro787Ala (c.2359C>G) is classified Benign/Likely benign in ARHGAP31 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-18). AlphaMissense: likely benign (0.0874); Rare (popmax 0.434%, afr); Associated with Inborn genetic diseases.

What condition is associated with ARHGAP31 p.Pro787Ala (c.2359C>G)?

ARHGAP31 p.Pro787Ala (c.2359C>G) is associated with Inborn genetic diseases, Adams-Oliver syndrome 1 (ClinVar).

How common is ARHGAP31 p.Pro787Ala (c.2359C>G) in the general population?

ARHGAP31 p.Pro787Ala (c.2359C>G) is rare (popmax 0.434%, afr) (gnomAD).

What do computational predictors say about ARHGAP31 p.Pro787Ala (c.2359C>G)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Pro787Ala

c.2359C>G · rs186621177 · VCV342656

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.434%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.87	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 0.83	GERP 2.6
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	13.76	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 0.434% African / African-American · 326/75,050 alleles

Filtering AF 0.395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.0228% 368/1,614,194 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.434%	230
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.0217%	4,618
Finnishnot grpmax-eligible	0.00468%	21,346
European (non-Finnish)	0.000339%	295,006

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: ARHGAP31
Protein: p.Pro787Ala
Coding: c.2359C>G
MANE Select: NM_020754
dbSNP: rs186621177
Type: single nucleotide variant
Location: chr3:119414288 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 787: the 'disordered' region

Full ARHGAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Adams-Oliver syndrome 1

Similar variants

ARHGAP31 p.Pro787Arg Uncertain significance ★ ⚠ same residue
ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same condition

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/arhgap31-p-pro787ala (accessed [today's date]).

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