Is ABCA3 p.Arg1331fs (c.3992_3993del) pathogenic?

ABCA3 p.Arg1331fs (c.39923993del) is classified Pathogenic in ABCA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-10). Very rare (popmax 0.00133%, afr).

How common is ABCA3 p.Arg1331fs (c.3992_3993del) in the general population?

ABCA3 p.Arg1331fs (c.3992_3993del) is very rare (popmax 0.00133%, afr) (gnomAD).

ABCA3 p.Arg1331fs

c.3992_3993del · rs2093657780 · VCV2910395

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 26 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,934 alleles

Overall 0.000657% 1/152,208 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: ABCA3
Protein: p.Arg1331fs
Coding: c.3992_3993del
MANE Select: NM_001089
dbSNP: rs2093657780
Type: Microsatellite
Location: chr16:2283228 (GRCh38)
Gene constraint: LOEUF 0.612 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.00 · 2 PDB

Full ABCA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA3 p.Leu1381fs Pathogenic ★★ same type
ABCA3 p.Phe1203del Pathogenic/Likely pathogenic ★★ same type
ABCA3 p.Ser577fs Pathogenic ★★ same type
ABCA3 p.Ser802fs Pathogenic ★★ same type
ABCA3 p.Glu891del Uncertain significance ★★ same type
ABCA3 p.Phe1635Ter Pathogenic ★ same type
ABCA3 p.Glu506_Asp507insGlu Uncertain significance ★ same type
ABCA3 p.Lys915del 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/abca3-p-arg1331fs (accessed [today's date]).

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