Is MTTP p.Gly730= (c.2190A>G) pathogenic?

MTTP p.Gly730= (c.2190A>G) is classified Likely benign in MTTP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-04). Very rare (popmax 0.00983%, nfe); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Gly730= (c.2190A>G)?

MTTP p.Gly730= (c.2190A>G) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Gly730= (c.2190A>G) in the general population?

MTTP p.Gly730= (c.2190A>G) is very rare (popmax 0.00983%, nfe) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Gly730=

c.2190A>G · rs761984561 · VCV763083

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00983%, 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 1.6	GERP -0.98, phastCons 1
Overall
CADD	7.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00983% European (non-Finnish) · 116/1,179,782 alleles

Filtering AF 0.00834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00776%

Overall 0.00731% 118/1,613,702 alleles · very rare exomes 113/1,461,528 · genomes 5/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00983%	10,171
Remaining individualsnot grpmax-eligible	0.0016%	62,466
African / African-American	0.00133%	74,918

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.Gly730=
Coding: c.2190A>G
MANE Select: NM_001386140
dbSNP: rs761984561
Type: single nucleotide variant
Location: chr4:99613113 (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 730: a β-strand

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.Gly730Val 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-gly730 (accessed [today's date]).

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