Is MTTP p.Arg46Gly (c.136C>G) pathogenic?

MTTP p.Arg46Gly (c.136C>G) is classified Benign/Likely benign in MTTP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0568); Low-frequency (popmax 3.92%, sas); Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Arg46Gly (c.136C>G)?

MTTP p.Arg46Gly (c.136C>G) is associated with abetalipoproteinemia (ClinVar).

How common is MTTP p.Arg46Gly (c.136C>G) in the general population?

MTTP p.Arg46Gly (c.136C>G) is low-frequency (popmax 3.92%, sas) (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.Arg46Gly (c.136C>G)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

MTTP p.Arg46Gly

c.136C>G · rs141736123 · VCV347020

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.92%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -3.07	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 1.3	GERP -1.2, phastCons 0.93
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	16.6	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 3.92% South Asian · 3,569/91,074 alleles

Filtering AF 3.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.77%

Overall 1.72% 27,807/1,614,112 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.92%	26
Middle Eastern	3.51%	28
Finnishnot grpmax-eligible	3.11%	32
European (non-Finnish)	1.71%	59
Remaining individualsnot grpmax-eligible	1.55%	65
Amishnot grpmax-eligible	1.54%	65
Admixed American	0.838%	119
Ashkenazi Jewishnot grpmax-eligible	0.645%	155
African / African-American	0.264%	379
East Asian	0.00891%	11,220

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.Arg46Gly
Coding: c.136C>G
MANE Select: NM_001386140
dbSNP: rs141736123
Type: single nucleotide variant
Location: chr4:99581979 (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 46: the vitellogenin domain

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.Arg46Trp Uncertain significance ★★ ⚠ same residue
MTTP p.Arg46Gln Uncertain significance ★ ⚠ same residue
MTTP p.Arg46Pro 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

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-arg46gly (accessed [today's date]).

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