Is MTTP p.Ala410fs (c.1229_1231delinsT) pathogenic?

MTTP p.Ala410fs (c.12291231delinsT) is classified Pathogenic in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ala410fs (c.1229_1231delinsT)?

MTTP p.Ala410fs (c.1229_1231delinsT) is associated with abetalipoproteinemia (ClinVar).

How is Abetalipoproteinemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MTTP p.Ala410fs

c.1229_1231delinsT · VCV4817985

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

abetalipoproteinemia

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 9 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.42, phastCons 0.99

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

Variant & gene context

Gene: MTTP
Protein: p.Ala410fs
Coding: c.1229_1231delinsT
MANE Select: NM_001386140
Type: Indel
Location: chr4:99600726 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB
Residue 410: the vitellogenin domain; an α-helix

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

Disease context

abetalipoproteinemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Abetalipoproteinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

MTTP p.Ala410Thr Uncertain significance ⚠ same residue
MTTP p.Ala758fs Likely pathogenic ★ same condition
MTTP p.Asn237delinsArgCysValTer Likely pathogenic ★ same condition
MTTP p.Asn685fs Likely pathogenic ★ same condition
MTTP p.Gly163fs Likely pathogenic ★ same condition
MTTP p.Phe767fs Likely pathogenic ★ same condition
MTTP p.Thr245fs Likely pathogenic ★ same condition
MTTP p.Ala410Asp Uncertain significance ★ ⚠ same residue

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/mttp-p-ala410fs (accessed [today's date]).

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