Is ARHGAP31 p.Thr511= (c.1533A>G) pathogenic?

ARHGAP31 p.Thr511= (c.1533A>G) is classified Benign in ARHGAP31 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Adams-Oliver syndrome 1.

What condition is associated with ARHGAP31 p.Thr511= (c.1533A>G)?

ARHGAP31 p.Thr511= (c.1533A>G) is associated with Adams-Oliver syndrome 1 (ClinVar).

ARHGAP31 p.Thr511=

Q: How common is ARHGAP31 p.Thr511= (c.1533A>G) in the general population?

ARHGAP31 p.Thr511= (c.1533A>G) is common (popmax 6.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1533A>G · rs77678258 · VCV342645

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.53%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -5.5
Overall
CADD	4.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.53% African / African-American · 4,898/74,966 alleles

Filtering AF 6.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.32%

Overall 0.38% 6,132/1,614,026 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.53%	15
Admixed American	0.665%	150
Remaining individualsnot grpmax-eligible	0.578%	173
Middle Eastern	0.544%	184
Ashkenazi Jewishnot grpmax-eligible	0.28%	357
European (non-Finnish)	0.0289%	3,460
South Asian	0.0187%	5,357

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.Thr511=
Coding: c.1533A>G
MANE Select: NM_020754
dbSNP: rs77678258
Type: single nucleotide variant
Location: chr3:119402285 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 511: the 'disordered' region

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.Thr511Ile Likely benign ★ same residue
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

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-thr511 (accessed [today's date]).

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