Is MTTP p.Asn685fs (c.2055delinsAGGCA) pathogenic?

MTTP p.Asn685fs (c.2055delinsAGGCA) is classified Likely pathogenic in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). Absent from gnomAD; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Asn685fs (c.2055delinsAGGCA)?

MTTP p.Asn685fs (c.2055delinsAGGCA) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Asn685fs (c.2055delinsAGGCA) in the general population?

MTTP p.Asn685fs (c.2055delinsAGGCA) 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.Asn685fs

c.2055delinsAGGCA · rs2476149064 · VCV1724636

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 0.78, 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.Asn685fs
Coding: c.2055delinsAGGCA
MANE Select: NM_001386140
dbSNP: rs2476149064
Type: Indel
Location: chr4:99612978 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB

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.Ala410fs Pathogenic ★ same condition
MTTP p.Ala758fs Likely pathogenic ★ same condition
MTTP p.Asn237delinsArgCysValTer 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.Asn685= Likely benign ★ same residue
MTTP c.1067+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-asn685fs (accessed [today's date]).

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