Is MTTP p.Glu98Asp (c.294G>C) pathogenic?

MTTP p.Glu98Asp (c.294G>C) is classified Benign/Likely benign in MTTP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0935); Common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Glu98Asp (c.294G>C)?

MTTP p.Glu98Asp (c.294G>C) is associated with abetalipoproteinemia (ClinVar).

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.Glu98Asp (c.294G>C)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

MTTP p.Glu98Asp

Q: How common is MTTP p.Glu98Asp (c.294G>C) in the general population?

MTTP p.Glu98Asp (c.294G>C) is common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.294G>C · rs2306986 · VCV347021

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 20.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

abetalipoproteinemia

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -3.24	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 0.32	GERP -2, phastCons 0.96
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic
Overall
CADD	13.49	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 20.9% East Asian · 9,378/44,828 alleles

Filtering AF 20.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.4%

Overall 5.09% 82,173/1,613,268 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	20.9%	5
African / African-American	19.4%	5
Middle Eastern	6.03%	17
Remaining individualsnot grpmax-eligible	5.77%	17
Admixed American	5.6%	18
Ashkenazi Jewishnot grpmax-eligible	5%	20
South Asian	4.11%	24
European (non-Finnish)	3.76%	27
Amishnot grpmax-eligible	3.62%	28
Finnishnot grpmax-eligible	2%	50

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.Glu98Asp
Coding: c.294G>C
MANE Select: NM_001386140
dbSNP: rs2306986
Type: single nucleotide variant
Location: chr4:99583418 (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 98: the vitellogenin domain; a UniProt-annotated variant site (in)

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-glu98asp (accessed [today's date]).

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