Is MTTP p.Tyr844= (c.2532C>T) pathogenic?

MTTP p.Tyr844= (c.2532C>T) is classified Likely benign in MTTP (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-30). Ultra-rare (popmax 0.0401%, eas); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Tyr844= (c.2532C>T)?

MTTP p.Tyr844= (c.2532C>T) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Tyr844= (c.2532C>T) in the general population?

MTTP p.Tyr844= (c.2532C>T) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Tyr844=

c.2532C>T · rs781654995 · VCV795391

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

Conditions

abetalipoproteinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.1	GERP -3.8
Overall
CADD	2.887	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,886 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0213%

Overall 0.00273% 44/1,613,746 alleles · ultra-rare exomes 42/1,461,712 · genomes 2/152,034 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,494
African / African-American	0.00802%	12,474
Admixed American	0.00333%	29,989
South Asian	0.0022%	45,541
European (non-Finnish)	0.00136%	73,742

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.Tyr844=
Coding: c.2532C>T
MANE Select: NM_001386140
dbSNP: rs781654995
Type: single nucleotide variant
Location: chr4:99622695 (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 844: 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 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-tyr844 (accessed [today's date]).

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