Is ARHGAP31 p.Pro1344Ser (c.4030C>T) pathogenic?

ARHGAP31 p.Pro1344Ser (c.4030C>T) is classified Uncertain significance in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely pathogenic (0.8754); Very rare (popmax 0.00768%, sas); Associated with Inborn genetic diseases.

What condition is associated with ARHGAP31 p.Pro1344Ser (c.4030C>T)?

ARHGAP31 p.Pro1344Ser (c.4030C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARHGAP31 p.Pro1344Ser (c.4030C>T) in the general population?

ARHGAP31 p.Pro1344Ser (c.4030C>T) is very rare (popmax 0.00768%, sas) (gnomAD).

What do computational predictors say about ARHGAP31 p.Pro1344Ser (c.4030C>T)?

AlphaMissense predicts likely pathogenic (score 0.8754) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Pro1344Ser

c.4030C>T · VCV3940153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8754	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000496% 8/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
European (non-Finnish)	8.47e-05%	1,180,034

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.Pro1344Ser
Coding: c.4030C>T
MANE Select: NM_020754
Type: single nucleotide variant
Location: chr3:119415959 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 1344: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARHGAP31 p.Pro1344= Likely benign ★ same residue
ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg510Ser Uncertain significance ★★ ⚠ 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-pro1344ser (accessed [today's date]).

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