Is ATL3 p.Asp528fs (c.1582dup) pathogenic?

ATL3 p.Asp528fs (c.1582dup) is classified Uncertain significance in ATL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). Very rare (popmax 0.000932%, nfe).

How common is ATL3 p.Asp528fs (c.1582dup) in the general population?

ATL3 p.Asp528fs (c.1582dup) is very rare (popmax 0.000932%, nfe) (gnomAD).

ATL3 p.Asp528fs

c.1582dup · rs774106436 · VCV2577115

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,030 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000752% 11/1,461,886 alleles · very rare

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: ATL3
Protein: p.Asp528fs
Coding: c.1582dup
MANE Select: NM_015459
dbSNP: rs774106436
Type: Duplication
Location: chr11:63629362 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB

Full ATL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATL3 p.Asp528Val Uncertain significance ★ ⚠ same residue
ATL3 p.Thr317fs Uncertain significance ★★ same type
ATL3 c.978+7dup Benign/Likely benign ★★ same type
ATL3 p.Ala355_Ala356insGluAlaAsnAsnLeuAlaAla Likely pathogenic ★ same type
ATL3 p.Gln52_Asp53insGlu Uncertain significance ★ same type
ATL3 p.Glu374fs Uncertain significance ★ same type
ATL3 p.Gly465fs Uncertain significance ★ same type
ATL3 p.Ile76fs 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/atl3-p-asp528fs (accessed [today's date]).

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