Is ARHGAP31 p.Leu128= (c.384G>C) pathogenic?

ARHGAP31 p.Leu128= (c.384G>C) is classified Benign/Likely benign in ARHGAP31 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-11). Low-frequency (popmax 1.61%, afr); Associated with Adams-Oliver syndrome 1.

What condition is associated with ARHGAP31 p.Leu128= (c.384G>C)?

ARHGAP31 p.Leu128= (c.384G>C) is associated with Adams-Oliver syndrome 1 (ClinVar).

How common is ARHGAP31 p.Leu128= (c.384G>C) in the general population?

ARHGAP31 p.Leu128= (c.384G>C) is low-frequency (popmax 1.61%, afr) (gnomAD).

ARHGAP31 p.Leu128=

c.384G>C · rs150339878 · VCV342629

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.61%, afr)

Conditions

Adams-Oliver syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -0.15, phastCons 1
Overall
CADD	9.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.61% African / African-American · 1,205/75,036 alleles

Filtering AF 1.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5%

Overall 0.104% 1,686/1,614,154 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.61%	62
Ashkenazi Jewishnot grpmax-eligible	0.851%	117
Remaining individualsnot grpmax-eligible	0.171%	584
Middle Eastern	0.132%	758
Admixed American	0.0916%	1,091
European (non-Finnish)	0.00483%	20,702
South Asian	0.0022%	45,543

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.Leu128=
Coding: c.384G>C
MANE Select: NM_020754
dbSNP: rs150339878
Type: single nucleotide variant
Location: chr3:119380939 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 128: the rho-gap domain

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-leu128 (accessed [today's date]).

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