Is MTTP p.Lys341= (c.1023A>G) pathogenic?

MTTP p.Lys341= (c.1023A>G) is classified Conflicting classifications of pathogenicity in MTTP (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-29). Rare (popmax 0.215%, mid); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Lys341= (c.1023A>G)?

MTTP p.Lys341= (c.1023A>G) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Lys341= (c.1023A>G) in the general population?

MTTP p.Lys341= (c.1023A>G) is rare (popmax 0.215%, mid) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Lys341=

c.1023A>G · rs145724674 · VCV347033

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.215%, mid)

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 -0.86, phastCons 1
Overall
CADD	6.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% Middle Eastern · 13/6,058 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0143% 231/1,614,030 alleles · rare exomes 175/1,461,706 · genomes 56/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.215%	466
African / African-American	0.076%	1,316
Admixed American	0.0283%	3,530
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)	0.0106%	9,439
South Asian	0.00659%	15,181
Finnishnot grpmax-eligible	0.00469%	21,339

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.Lys341=
Coding: c.1023A>G
MANE Select: NM_001386140
dbSNP: rs145724674
Type: single nucleotide variant
Location: chr4:99597180 (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 341: the vitellogenin domain; 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 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-lys341 (accessed [today's date]).

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