Is ARHGAP31 p.Leu918Phe (c.2752C>T) pathogenic?

ARHGAP31 p.Leu918Phe (c.2752C>T) is classified Uncertain significance in ARHGAP31 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-28). AlphaMissense: likely pathogenic (0.796); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARHGAP31 p.Leu918Phe (c.2752C>T)?

ARHGAP31 p.Leu918Phe (c.2752C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARHGAP31 p.Leu918Phe (c.2752C>T) in the general population?

ARHGAP31 p.Leu918Phe (c.2752C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP31 p.Leu918Phe (c.2752C>T)?

AlphaMissense predicts likely pathogenic (score 0.796) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Leu918Phe

c.2752C>T · rs1327129629 · VCV2118404

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.796 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.796	likely pathogenic
REVEL	0.153	moderately benign-leaning
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP31
Protein: p.Leu918Phe
Coding: c.2752C>T
MANE Select: NM_020754
dbSNP: rs1327129629
Type: single nucleotide variant
Location: chr3:119414681 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 918: 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.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
ARHGAP31 p.Arg950Cys 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-leu918phe (accessed [today's date]).

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