Is MTTP p.Leu811Phe (c.2433G>C) pathogenic?

MTTP p.Leu811Phe (c.2433G>C) is classified Conflicting classifications of pathogenicity in MTTP (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.1632); Rare (popmax 0.693%, mid); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Leu811Phe (c.2433G>C)?

MTTP p.Leu811Phe (c.2433G>C) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Leu811Phe (c.2433G>C) in the general population?

MTTP p.Leu811Phe (c.2433G>C) is rare (popmax 0.693%, mid) (gnomAD).

How is Abetalipoproteinemia inherited?

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

What do computational predictors say about MTTP p.Leu811Phe (c.2433G>C)?

AlphaMissense predicts likely benign (score 0.1632) — an in-silico prediction, not a clinical call.

MTTP p.Leu811Phe

c.2433G>C · rs144590904 · VCV285288

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.1632 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.693%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.1632	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -4.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.73, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	18.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.693% Middle Eastern · 42/6,062 alleles

Filtering AF 0.527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.161% 2,601/1,614,034 alleles · rare exomes 2,386/1,461,780 · genomes 215/152,254 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.693%	144
Admixed American	0.323%	309
Remaining individualsnot grpmax-eligible	0.23%	434
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
European (non-Finnish)	0.172%	582
South Asian	0.11%	911
African / African-American	0.0373%	2,679
Finnishnot grpmax-eligible	0.00156%	64,018

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.Leu811Phe
Coding: c.2433G>C
MANE Select: NM_001386140
dbSNP: rs144590904
Type: single nucleotide variant
Location: chr4:99621151 (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.Leu811= 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
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-leu811phe (accessed [today's date]).

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