Is ARHGAP31 p.Asp889= (c.2667C>T) pathogenic?

ARHGAP31 p.Asp889= (c.2667C>T) is classified Benign/Likely benign in ARHGAP31 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-04). Rare (popmax 0.132%, afr).

How common is ARHGAP31 p.Asp889= (c.2667C>T) in the general population?

ARHGAP31 p.Asp889= (c.2667C>T) is rare (popmax 0.132%, afr) (gnomAD).

ARHGAP31 p.Asp889=

c.2667C>T · rs140312580 · VCV2191878

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, afr)

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 -5.5	GERP -4.8
Overall
CADD	2.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% African / African-American · 99/75,030 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0075% 121/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.132%	758
Middle Eastern	0.033%	3,031
Admixed American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00119%	84,289

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.Asp889=
Coding: c.2667C>T
MANE Select: NM_020754
dbSNP: rs140312580
Type: single nucleotide variant
Location: chr3:119414596 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 889: the 'disordered' region

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

Similar variants

ARHGAP31 p.Asp889Glu Uncertain significance ★ ⚠ same residue
ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same type

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-asp889 (accessed [today's date]).

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