Is ARPC4 p.Asp80Glu (c.240T>G) pathogenic?

ARPC4 p.Asp80Glu (c.240T>G) is classified Uncertain significance in ARPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: likely pathogenic (0.9967); Rare (popmax 0.105%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARPC4 p.Asp80Glu (c.240T>G)?

ARPC4 p.Asp80Glu (c.240T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC4 p.Asp80Glu (c.240T>G) in the general population?

ARPC4 p.Asp80Glu (c.240T>G) is rare (popmax 0.105%, nfe) (gnomAD).

What do computational predictors say about ARPC4 p.Asp80Glu (c.240T>G)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

ARPC4 p.Asp80Glu

c.240T>G · rs2471939746 · VCV3129755

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic
REVEL	0.321	indeterminate
SaProt	LLR -12.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.81, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 13 kb · p 7.2e-15 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.105% European (non-Finnish) · 1,230/1,166,180 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0985%

Overall 0.0851% 1,359/1,596,250 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.105%	948
Middle Eastern	0.0827%	1,209
Remaining individualsnot grpmax-eligible	0.0711%	1,407
Ashkenazi Jewishnot grpmax-eligible	0.0447%	2,237
South Asian	0.0356%	2,805
African / African-American	0.0281%	3,556
East Asian	0.0112%	8,940
Finnishnot grpmax-eligible	0.00786%	12,724
Admixed American	0.00674%	14,839

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: ARPC4
Protein: p.Asp80Glu
Coding: c.240T>G
MANE Select: NM_005718
dbSNP: rs2471939746
Type: single nucleotide variant
Location: chr3:9801666 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.20 · 5 PDB

Full ARPC4 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

ARPC4 c.3+11C>G Uncertain significance ★ same condition
ARPC4 c.3+11C>T Uncertain significance ★ same condition
ARPC4 c.3+16C>T Uncertain significance ★ same condition
ARPC4 c.3+17C>A Uncertain significance ★ same condition
ARPC4 c.3+20G>A Uncertain significance ★ same condition
ARPC4 c.3+38G>A Uncertain significance ★ same condition
ARPC4 c.3+47C>T Uncertain significance ★ same condition
ARPC4 c.3+55T>G 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/arpc4-p-asp80glu (accessed [today's date]).

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