Is MTTP p.Glu134fs (c.399dup) pathogenic?

MTTP p.Glu134fs (c.399dup) is classified Pathogenic/Likely pathogenic in MTTP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-19). Absent from gnomAD; Associated with MTTP-related disorder.

What condition is associated with MTTP p.Glu134fs (c.399dup)?

MTTP p.Glu134fs (c.399dup) is associated with MTTP-related disorder (ClinVar).

How common is MTTP p.Glu134fs (c.399dup) in the general population?

MTTP p.Glu134fs (c.399dup) is absent from gnomAD (gnomAD).

MTTP p.Glu134fs

c.399dup · rs1190052366 · VCV2154056

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

MTTP-related disorder

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 4 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP 0.76, phastCons 1

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.Glu134fs
Coding: c.399dup
MANE Select: NM_001386140
dbSNP: rs1190052366
Type: Duplication
Location: chr4:99589645 (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 134: the vitellogenin domain; a β-strand

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

Disease context

MTTP-related disorder

Similar variants

MTTP p.Glu134Ter Pathogenic/Likely pathogenic ★★ same residue
MTTP p.Asn140fs Pathogenic ★★ same condition
MTTP p.Thr787fs Likely pathogenic ★ same condition
MTTP p.Val854fs Likely pathogenic ★ same condition
MTTP c.1236+1G>A Pathogenic/Likely pathogenic ★★ same condition
MTTP c.1867+1G>A Pathogenic ★★ same condition
MTTP c.1867+5G>A Pathogenic/Likely pathogenic ★★ same condition
MTTP c.619-1G>C 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-glu134fs (accessed [today's date]).

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