Is ARHGAP31 c.682+19A>C pathogenic?

ARHGAP31 c.682+19A>C is classified Benign in ARHGAP31 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Adams-Oliver syndrome 1.

What condition is associated with ARHGAP31 c.682+19A>C?

ARHGAP31 c.682+19A>C is associated with Adams-Oliver syndrome 1 (ClinVar).

ARHGAP31 c.682+19A>C

Q: How common is ARHGAP31 c.682+19A>C in the general population?

ARHGAP31 c.682+19A>C is common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs72966429 · VCV1167309

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 5.27%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Adams-Oliver syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +19	near-intronic (+19 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.087	GERP -3.2
Non-coding constraint	Z 0.44	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	0.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.27% African / African-American · 3,951/75,002 alleles

Filtering AF 5.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.07%

Overall 0.333% 5,379/1,613,886 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.27%	19
Middle Eastern	0.794%	126
Ashkenazi Jewishnot grpmax-eligible	0.564%	177
Admixed American	0.437%	229
Remaining individualsnot grpmax-eligible	0.422%	237
European (non-Finnish)	0.0565%	1,769
South Asian	0.0198%	5,060
Finnishnot grpmax-eligible	0.00313%	31,996

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
Coding: c.682+19A>C
MANE Select: NM_020754
dbSNP: rs72966429
Type: single nucleotide variant
Location: chr3:119383245 (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-c-682-plus-19a-c (accessed [today's date]).

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