Is ARHGAP31 p.Glu488Gln (c.1462G>C) pathogenic?

ARHGAP31 p.Glu488Gln (c.1462G>C) is classified Uncertain significance in ARHGAP31 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.5131); Very rare (popmax 0.00237%, nfe); Associated with Adams-Oliver syndrome 1.

What condition is associated with ARHGAP31 p.Glu488Gln (c.1462G>C)?

ARHGAP31 p.Glu488Gln (c.1462G>C) is associated with Adams-Oliver syndrome 1 (ClinVar).

How common is ARHGAP31 p.Glu488Gln (c.1462G>C) in the general population?

ARHGAP31 p.Glu488Gln (c.1462G>C) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about ARHGAP31 p.Glu488Gln (c.1462G>C)?

AlphaMissense predicts ambiguous (score 0.5131) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Glu488Gln

c.1462G>C · rs1010908062 · VCV2672252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5131 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Adams-Oliver syndrome 1

Computational evidence

Protein change
AlphaMissense	0.5131	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.30	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 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	24.2	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 0.00237% European (non-Finnish) · 28/1,180,054 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00173% 28/1,614,132 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: ARHGAP31
Protein: p.Glu488Gln
Coding: c.1462G>C
MANE Select: NM_020754
dbSNP: rs1010908062
Type: single nucleotide variant
Location: chr3:119402214 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32

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

Disease context

Adams-Oliver syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Gln1233Leu Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.His48Tyr Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Lys449Glu Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Trp304Ter Uncertain significance ★★ same condition
ARHGAP31 c.100+77A>T Benign ★★ same condition
ARHGAP31 c.1070-92G>C Benign ★★ same condition
ARHGAP31 c.1926+11T>C Benign ★★ 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-glu488gln (accessed [today's date]).

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