Is MTTP p.Gly151= (c.453T>C) pathogenic?

MTTP p.Gly151= (c.453T>C) is classified Benign in MTTP (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 76.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Gly151= (c.453T>C)?

MTTP p.Gly151= (c.453T>C) is associated with abetalipoproteinemia (ClinVar).

How is Abetalipoproteinemia inherited?

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

MTTP p.Gly151=

Q: How common is MTTP p.Gly151= (c.453T>C) in the general population?

MTTP p.Gly151= (c.453T>C) is common (popmax 76.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.453T>C · rs991811 · VCV129625

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 76.5%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.17	GERP 0.82, phastCons 0.037
Overall
CADD	8.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 76.5% African / African-American · 57,021/74,516 alleles

Filtering AF 76% ClinGen BA1/BS1 input FAF95, joint · FAF99 75.8%

Overall 38.5% 617,277/1,603,712 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	76.5%	1
East Asian	67.1%	1
Ashkenazi Jewishnot grpmax-eligible	57.4%	2
Middle Eastern	51.4%	2
Amishnot grpmax-eligible	46.9%	2
South Asian	42.1%	2
Remaining individualsnot grpmax-eligible	40.5%	2
European (non-Finnish)	35.4%	3
Admixed American	30%	3
Finnishnot grpmax-eligible	20.9%	5

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.Gly151=
Coding: c.453T>C
MANE Select: NM_001386140
dbSNP: rs991811
Type: single nucleotide variant
Location: chr4:99589702 (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 151: 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 p.Gly151Ser Uncertain significance ★★ ⚠ same residue
MTTP p.Gly151Val 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

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-gly151 (accessed [today's date]).

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