Is ART4 p.Asp56Asn (c.166G>A) pathogenic?

ART4 p.Asp56Asn (c.166G>A) is classified Uncertain significance in ART4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.1012); Very rare (popmax 0.00206%, amr).

How common is ART4 p.Asp56Asn (c.166G>A) in the general population?

ART4 p.Asp56Asn (c.166G>A) is very rare (popmax 0.00206%, amr) (gnomAD).

What do computational predictors say about ART4 p.Asp56Asn (c.166G>A)?

AlphaMissense predicts likely benign (score 0.1012) — an in-silico prediction, not a clinical call.

ART4 p.Asp56Asn

c.166G>A · rs775874295 · VCV3129960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1012 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00206%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1012	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -6.07	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 1.7	GERP -1.9, phastCons 0.97
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.58 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.00206% Admixed American · 1/48,592 alleles

Filtering AF 0.000624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000481%

Overall 0.00108% 17/1,571,064 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00206%	48,592
Remaining individualsnot grpmax-eligible	0.00165%	60,434
African / African-American	0.00138%	72,454
South Asian	0.00118%	84,760
European (non-Finnish)	0.00112%	89,476

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: ART4
Protein: p.Asp56Asn
Coding: c.166G>A
MANE Select: NM_021071
dbSNP: rs775874295
Type: single nucleotide variant
Location: chr12:14841132 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00

Full ART4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ART4 p.Ala103Val Uncertain significance ★ ⚠ same type
ART4 p.Ala20Ser Uncertain significance ★ ⚠ same type
ART4 p.Ala50Thr Uncertain significance ★ ⚠ same type
ART4 p.Ala58Thr Uncertain significance ★ ⚠ same type
ART4 p.Arg171Lys Uncertain significance ★ ⚠ same type
ART4 p.Arg171Thr Uncertain significance ★ ⚠ same type
ART4 p.Arg263Gly Uncertain significance ★ ⚠ same type
ART4 p.Asn257Ser Uncertain significance ★ ⚠ same type

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/art4-p-asp56asn (accessed [today's date]).

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