Is MTTP p.Ser13= (c.39C>G) pathogenic?

MTTP p.Ser13= (c.39C>G) is classified Benign in MTTP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with abetalipoproteinemia.

What condition is associated with MTTP p.Ser13= (c.39C>G)?

MTTP p.Ser13= (c.39C>G) is associated with abetalipoproteinemia (ClinVar).

How is Abetalipoproteinemia inherited?

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

MTTP p.Ser13=

Q: How common is MTTP p.Ser13= (c.39C>G) in the general population?

MTTP p.Ser13= (c.39C>G) is common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.39C>G · rs7667001 · VCV347019

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 16.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

abetalipoproteinemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.88	GERP -1.9, phastCons 0.002
Overall
CADD	9.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.4% African / African-American · 12,276/74,968 alleles

Filtering AF 16.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 16%

Overall 4.54% 73,258/1,613,968 alleles · common exomes 62,405/1,461,784 · genomes 10,853/152,184 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.4%	6
Ashkenazi Jewishnot grpmax-eligible	5.22%	19
Remaining individualsnot grpmax-eligible	4.95%	20
Middle Eastern	4.69%	21
Finnishnot grpmax-eligible	4.23%	24
European (non-Finnish)	4.09%	24
Admixed American	3.89%	26
South Asian	3.04%	33
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00668%	14,961

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.Ser13=
Coding: c.39C>G
MANE Select: NM_001386140
dbSNP: rs7667001
Type: single nucleotide variant
Location: chr4:99574948 (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 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-ser13 (accessed [today's date]).

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