Is MTTP p.Ile547fs (c.1636_1637dup) pathogenic?

MTTP p.Ile547fs (c.16361637dup) is classified Pathogenic/Likely pathogenic in MTTP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-01). Absent from gnomAD; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ile547fs (c.1636_1637dup)?

MTTP p.Ile547fs (c.1636_1637dup) is associated with abetalipoproteinemia, metabolic syndrome X (ClinVar).

How common is MTTP p.Ile547fs (c.1636_1637dup) in the general population?

MTTP p.Ile547fs (c.1636_1637dup) is absent from gnomAD (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Ile547fs

c.1636_1637dup · rs2110230146 · VCV1385779

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 1.6, phastCons 0.23

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MTTP
Protein: p.Ile547fs
Coding: c.1636_1637dup
MANE Select: NM_001386140
dbSNP: rs2110230146
Type: Duplication
Location: chr4:99608842 (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 547: 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

Also linked: metabolic syndrome X

For Abetalipoproteinemia (Orphanet):

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

Similar variants

MTTP p.Asn140fs Pathogenic ★★ same condition
MTTP p.Glu443Ter Likely pathogenic ★ same condition
MTTP p.Leu26fs Likely pathogenic ★ same condition
MTTP p.Leu79fs Likely pathogenic ★ same condition
MTTP p.Ser861fs Likely pathogenic ★ same condition
MTTP p.Ile547Thr Uncertain significance ★ ⚠ same residue
MTTP c.1067+1G>C Likely pathogenic ★★ same condition
MTTP c.1769+2T>C Pathogenic/Likely pathogenic ★★ 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/mttp-p-ile547fs (accessed [today's date]).

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