Is ARPC5 p.Arg47Leu (c.140G>T) pathogenic?

ARPC5 p.Arg47Leu (c.140G>T) is classified Uncertain significance in ARPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.7684); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARPC5 p.Arg47Leu (c.140G>T)?

ARPC5 p.Arg47Leu (c.140G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC5 p.Arg47Leu (c.140G>T) in the general population?

ARPC5 p.Arg47Leu (c.140G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARPC5 p.Arg47Leu (c.140G>T)?

AlphaMissense predicts likely pathogenic (score 0.7684) — an in-silico prediction, not a clinical call.

ARPC5 p.Arg47Leu

c.140G>T · VCV4148107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7684 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7684	likely pathogenic
REVEL	0.282	benign-leaning
SaProt	LLR -13.27	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 8,037 bp · p 0.0083 · regional, not allelic
Overall
CADD	23.4	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: ARPC5
Protein: p.Arg47Leu
Coding: c.140G>T
MANE Select: NM_005717
Type: single nucleotide variant
Location: chr1:183635520 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 92.42 · 2 PDB
Residue 47: a UniProt-annotated variant site (in imd113; likely pathogenic; loss of protein expression in patient cells)

Full ARPC5 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

ARPC5 p.Ala54Thr Uncertain significance ★ ⚠ same condition
ARPC5 p.Asn101Ser Uncertain significance ★ ⚠ same condition
ARPC5 p.Asn61Ser Uncertain significance ★ ⚠ same condition
ARPC5 p.Asp104Gly Uncertain significance ★ ⚠ same condition
ARPC5 p.Asp32Glu Uncertain significance ★ ⚠ same condition
ARPC5 p.Ile78Val Uncertain significance ★ ⚠ same condition
ARPC5 p.Ile84Leu Uncertain significance ★ ⚠ same condition
ARPC5 p.Leu106Pro 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/arpc5-p-arg47leu (accessed [today's date]).

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