Is MTTP p.Asp169Val (c.506A>T) pathogenic?

MTTP p.Asp169Val (c.506A>T) is classified Likely pathogenic in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). AlphaMissense: likely pathogenic (0.9703); Absent from gnomAD v4.1; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Asp169Val (c.506A>T)?

MTTP p.Asp169Val (c.506A>T) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Asp169Val (c.506A>T) in the general population?

MTTP p.Asp169Val (c.506A>T) is absent from gnomAD v4.1 (gnomAD).

How is Abetalipoproteinemia inherited?

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

What do computational predictors say about MTTP p.Asp169Val (c.506A>T)?

AlphaMissense predicts likely pathogenic (score 0.9703) — an in-silico prediction, not a clinical call.

MTTP p.Asp169Val

c.506A>T · VCV4817993

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9703 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.9703	likely pathogenic ✓ concordant with ClinVar · top 2% in MTTP
REVEL	0.718	pathogenic-leaning
SaProt	LLR -12.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.25	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MTTP
Protein: p.Asp169Val
Coding: c.506A>T
MANE Select: NM_001386140
Type: single nucleotide variant
Location: chr4:99591239 (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 169: a UniProt-annotated variant site (in abl; no loss on localization to the endoplasmic reticulum; does not reduce interaction with apob; inhibits interaction with p4hb/pdi; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein b secretion); the vitellogenin domain; a β-strand

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.Asp169= Likely benign ★ same residue
MTTP c.1067+1G>C Likely pathogenic ★★ same condition
MTTP c.1769+2T>C 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.1868-2A>G Likely pathogenic ★★ same condition
MTTP c.2342+1G>A Pathogenic ★★ same condition
MTTP c.502-1G>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-asp169val (accessed [today's date]).

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