Is ARHGAP31 p.Ser1323Phe (c.3968C>T) pathogenic?

ARHGAP31 p.Ser1323Phe (c.3968C>T) is classified Uncertain significance in ARHGAP31 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-17). AlphaMissense: likely benign (0.2284); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARHGAP31 p.Ser1323Phe (c.3968C>T)?

ARHGAP31 p.Ser1323Phe (c.3968C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARHGAP31 p.Ser1323Phe (c.3968C>T) in the general population?

ARHGAP31 p.Ser1323Phe (c.3968C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP31 p.Ser1323Phe (c.3968C>T)?

AlphaMissense predicts likely benign (score 0.2284) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Ser1323Phe

c.3968C>T · rs2472879266 · VCV1993145

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2284 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2284	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser1323Phe
Coding: c.3968C>T
MANE Select: NM_020754
dbSNP: rs2472879266
Type: single nucleotide variant
Location: chr3:119415897 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 1323: 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.Ser1323Ala Uncertain significance ★ ⚠ 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-ser1323phe (accessed [today's date]).

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