Is MTTP p.Ser383= (c.1149T>C) pathogenic?

MTTP p.Ser383= (c.1149T>C) is classified Likely benign in MTTP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0169%, nfe); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ser383= (c.1149T>C)?

MTTP p.Ser383= (c.1149T>C) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Ser383= (c.1149T>C) in the general population?

MTTP p.Ser383= (c.1149T>C) is ultra-rare (popmax 0.0169%, nfe) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Ser383=

c.1149T>C · rs374820674 · VCV777146

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, nfe)

Conditions

abetalipoproteinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP 0.083
Overall
CADD	7.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% European (non-Finnish) · 199/1,179,832 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0132% 213/1,613,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0169%	5,929
Remaining individualsnot grpmax-eligible	0.0112%	8,925
Admixed American	0.01%	9,998
African / African-American	0.00133%	74,912

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MTTP
Protein: p.Ser383=
Coding: c.1149T>C
MANE Select: NM_001386140
dbSNP: rs374820674
Type: single nucleotide variant
Location: chr4:99600646 (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 383: the vitellogenin domain

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 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
MTTP c.502-2A>G 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-ser383 (accessed [today's date]).

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