Is MTTP p.Ala577= (c.1731C>T) pathogenic?

MTTP p.Ala577= (c.1731C>T) is classified Benign/Likely benign in MTTP (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-02). Rare (popmax 0.918%, afr); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ala577= (c.1731C>T)?

MTTP p.Ala577= (c.1731C>T) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Ala577= (c.1731C>T) in the general population?

MTTP p.Ala577= (c.1731C>T) is rare (popmax 0.918%, afr) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Ala577=

c.1731C>T · rs112506924 · VCV284227

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.918%, afr)

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 -0.41	GERP -0.12
Overall
CADD	8.604	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.918% African / African-American · 689/75,036 alleles

Filtering AF 0.861% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.839%

Overall 0.0467% 753/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.918%	109
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Admixed American	0.0233%	4,288
South Asian	0.0022%	45,534
European (non-Finnish)	0.00102%	98,332

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.Ala577=
Coding: c.1731C>T
MANE Select: NM_001386140
dbSNP: rs112506924
Type: single nucleotide variant
Location: chr4:99608939 (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 577: 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.Ala577Thr 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-ala577 (accessed [today's date]).

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