Is MTTP p.Asp384Ala (c.1151A>C) pathogenic?

MTTP p.Asp384Ala (c.1151A>C) is classified Benign/Likely benign in MTTP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0965); Common (popmax 15.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Asp384Ala (c.1151A>C)?

MTTP p.Asp384Ala (c.1151A>C) is associated with abetalipoproteinemia (ClinVar).

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.Asp384Ala (c.1151A>C)?

AlphaMissense predicts likely benign (score 0.0965) — an in-silico prediction, not a clinical call.

MTTP p.Asp384Ala

Q: How common is MTTP p.Asp384Ala (c.1151A>C) in the general population?

MTTP p.Asp384Ala (c.1151A>C) is common (popmax 15.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1151A>C · rs17029215 · VCV283193

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0965 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.7%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.0965	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.5, phastCons 0.006
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	11.69	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

Grpmax group 15.7% African / African-American · 11,753/74,982 alleles

Filtering AF 15.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.3%

Overall 4.52% 72,935/1,613,764 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.7%	6
Ashkenazi Jewishnot grpmax-eligible	5.2%	19
Finnishnot grpmax-eligible	5.16%	19
Remaining individualsnot grpmax-eligible	4.94%	20
Middle Eastern	4.66%	21
European (non-Finnish)	4.06%	25
Admixed American	3.85%	26
South Asian	3.03%	33
Amishnot grpmax-eligible	0.11%	910
East Asian	0.00669%	14,954

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.Asp384Ala
Coding: c.1151A>C
MANE Select: NM_001386140
dbSNP: rs17029215
Type: single nucleotide variant
Location: chr4:99600648 (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 384: a UniProt-annotated variant site (no loss on localization to the endoplasmic reticulum; does not reduce interaction with p4hb/pdi; reduces phospholipid or triglyceride transfer activity; does not inhibit apolipoprotein b secretion); 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 p.Asp384Asn 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-asp384ala (accessed [today's date]).

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