Is MTTP p.Arg777Ter (c.2329C>T) pathogenic?

MTTP p.Arg777Ter (c.2329C>T) is classified Pathogenic/Likely pathogenic in MTTP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-22). Very rare (popmax 0.00334%, amr); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Arg777Ter (c.2329C>T)?

MTTP p.Arg777Ter (c.2329C>T) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Arg777Ter (c.2329C>T) in the general population?

MTTP p.Arg777Ter (c.2329C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

How is Abetalipoproteinemia inherited?

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

MTTP p.Arg777Ter

c.2329C>T · rs777548973 · VCV956573

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

abetalipoproteinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.8, phastCons 0.79
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,964 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000372% 6/1,613,002 alleles · very rare exomes 5/1,461,088 · genomes 1/151,914 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,982
East Asian	0.00223%	44,828
South Asian	0.0011%	91,040
European (non-Finnish)	0.00017%	589,703

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.Arg777Ter
Coding: c.2329C>T
MANE Select: NM_001386140
dbSNP: rs777548973
Type: single nucleotide variant
Location: chr4:99619085 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.73 · 2 PDB

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.Arg777Gln Uncertain significance ★★ ⚠ same residue
MTTP p.Arg777Leu Uncertain significance ★★ ⚠ same residue
MTTP p.Arg777= Likely benign ★ 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

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-arg777ter (accessed [today's date]).

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