Is ARHGAP31 p.Ser1078= (c.3234C>T) pathogenic?

ARHGAP31 p.Ser1078= (c.3234C>T) is classified Likely benign in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-25). Very rare (popmax 0.00167%, amr).

How common is ARHGAP31 p.Ser1078= (c.3234C>T) in the general population?

ARHGAP31 p.Ser1078= (c.3234C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

ARHGAP31 p.Ser1078=

c.3234C>T · rs958230823 · VCV1967745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.21	GERP -2.5
Overall
CADD	0.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,034 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00041% 6/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,034
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000339%	295,010

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.Ser1078=
Coding: c.3234C>T
MANE Select: NM_020754
dbSNP: rs958230823
Type: single nucleotide variant
Location: chr3:119415163 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 1078: the 'disordered' region

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

Similar variants

ARHGAP31 p.Ser1078Thr 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-ser1078 (accessed [today's date]).

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