Is MTTP p.Lys879Arg (c.2636A>G) pathogenic?

MTTP p.Lys879Arg (c.2636A>G) is classified Benign/Likely benign in MTTP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0641); Low-frequency (popmax 3.17%, afr); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Lys879Arg (c.2636A>G)?

MTTP p.Lys879Arg (c.2636A>G) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Lys879Arg (c.2636A>G) in the general population?

MTTP p.Lys879Arg (c.2636A>G) is low-frequency (popmax 3.17%, afr) (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.Lys879Arg (c.2636A>G)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

MTTP p.Lys879Arg

c.2636A>G · rs114049933 · VCV347045

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.17%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.52	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 3.5	GERP -3.8, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	15.53	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 3.17% African / African-American · 2,381/75,024 alleles

Filtering AF 3.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.02%

Overall 0.181% 2,925/1,614,110 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.17%	32
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.275%	363
Admixed American	0.235%	426
Ashkenazi Jewishnot grpmax-eligible	0.149%	673
European (non-Finnish)	0.0136%	7,375
South Asian	0.00878%	11,385
Finnishnot grpmax-eligible	0.00156%	64,042

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.Lys879Arg
Coding: c.2636A>G
MANE Select: NM_001386140
dbSNP: rs114049933
Type: single nucleotide variant
Location: chr4:99622799 (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 879: a turn

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-lys879arg (accessed [today's date]).

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