Is ABCA2 p.Ala2138fs (c.6412_6415del) pathogenic?

ABCA2 p.Ala2138fs (c.64126415del) is classified Likely pathogenic in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-02). Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

ABCA2 p.Ala2138fs

Q: What condition is associated with ABCA2 p.Ala2138fs (c.6412_6415del)?

ABCA2 p.Ala2138fs (c.6412_6415del) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.6412_6415del · VCV4891159

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual developmental disorder with poor growth and with or without seizures or ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 42 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 0.99, phastCons 1

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

Variant & gene context

Gene: ABCA2
Protein: p.Ala2138fs
Coding: c.6412_6415del
MANE Select: NM_001606
Type: Deletion
Location: chr9:137010063 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 2138: the abc transporter 2 domain; a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with poor growth and with or without seizures or ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA2 c.6630_6630+1del Pathogenic ★★ same condition
ABCA2 p.Arg1362_Thr1367del Uncertain significance ★★ same condition
ABCA2 p.Leu283fs Likely pathogenic ★ same condition
ABCA2 p.Met225fs Pathogenic ★ same condition
ABCA2 p.Ser617fs Pathogenic ★ same condition
ABCA2 p.Ala2138Val Uncertain significance ★ ⚠ same residue
ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala367Thr 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/abca2-p-ala2138fs (accessed [today's date]).

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