Is MTTP p.Ser590Ile (c.1769G>T) pathogenic?

MTTP p.Ser590Ile (c.1769G>T) is classified Pathogenic in MTTP (ClinVar, No assertion criteria, 2 submitters; last evaluated 2003-02-01). AlphaMissense: ambiguous (0.5626); Absent from gnomAD v4.1; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ser590Ile (c.1769G>T)?

MTTP p.Ser590Ile (c.1769G>T) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Ser590Ile (c.1769G>T) in the general population?

MTTP p.Ser590Ile (c.1769G>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.Ser590Ile (c.1769G>T)?

AlphaMissense predicts ambiguous (score 0.5626) — an in-silico prediction, not a clinical call.

MTTP p.Ser590Ile

c.1769G>T · rs199422222 · VCV14241

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5626 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,824)

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.5626	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -12.11	damaging
Splicing
SpliceAI	Δ0.72	donor loss · deltas
Pangolin	Δ0.76	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,608,824). 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.Ser590Ile
Coding: c.1769G>T
MANE Select: NM_001386140
dbSNP: rs199422222
Type: single nucleotide variant
Location: chr4:99608977 (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 590: the vitellogenin domain; a UniProt-annotated variant site (in abl; no loss on localization to the endoplasmic reticulum; does not reduce interaction with p4hb/pdi; inhibits phospholipid or triglyceride transfer activity; inhibits apolipoprotein b secretion); 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.Ser590Asn Uncertain significance ★ ⚠ 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-ser590ile (accessed [today's date]).

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