Is MTTP p.Ser738fs (c.2212del) pathogenic?

MTTP p.Ser738fs (c.2212del) is classified Pathogenic/Likely pathogenic in MTTP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-02). Very rare (popmax 0.00017%, nfe); Associated with MTTP-related disorder.

What condition is associated with MTTP p.Ser738fs (c.2212del)?

MTTP p.Ser738fs (c.2212del) is associated with MTTP-related disorder, abetalipoproteinemia (ClinVar).

How common is MTTP p.Ser738fs (c.2212del) in the general population?

MTTP p.Ser738fs (c.2212del) is very rare (popmax 0.00017%, nfe) (gnomAD).

MTTP p.Ser738fs

c.2212del · rs755681036 · VCV495776

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

MTTP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,806 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000342% 5/1,460,148 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,858
European (non-Finnish)grpmax	0.00017%	589,404

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser738fs
Coding: c.2212del
MANE Select: NM_001386140
dbSNP: rs755681036
Type: Deletion
Location: chr4:99613134 (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

MTTP-related disorder

Also linked: abetalipoproteinemia

Similar variants

MTTP p.Ala214fs Pathogenic ★★ same condition
MTTP p.Asp224fs Pathogenic/Likely pathogenic ★★ same condition
MTTP p.Glu462fs Likely pathogenic ★★ same condition
MTTP p.Glu465fs Pathogenic/Likely pathogenic ★★ same condition
MTTP p.Gly49fs Pathogenic/Likely pathogenic ★★ same condition
MTTP p.Ile650fs Pathogenic/Likely pathogenic ★★ same condition
MTTP p.Leu125fs Pathogenic/Likely pathogenic ★★ same condition
MTTP p.Phe399fs Pathogenic/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-ser738fs (accessed [today's date]).

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