Is MTTP p.Lys35fs (c.103_127del) pathogenic?

MTTP p.Lys35fs (c.103127del) is classified Pathogenic in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-10). Absent from gnomAD.

How common is MTTP p.Lys35fs (c.103_127del) in the general population?

MTTP p.Lys35fs (c.103_127del) is absent from gnomAD (gnomAD).

MTTP p.Lys35fs

c.103_127del · rs2476086722 · VCV2418922

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 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

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MTTP
Protein: p.Lys35fs
Coding: c.103_127del
MANE Select: NM_001386140
dbSNP: rs2476086722
Type: Deletion
Location: chr4:99581945 (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 35: the vitellogenin domain; a β-strand

Full MTTP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MTTP p.Ala214fs Pathogenic ★★ same type
MTTP p.Asp224fs Pathogenic/Likely pathogenic ★★ same type
MTTP p.Glu462fs Likely pathogenic ★★ same type
MTTP p.Glu465fs Pathogenic/Likely pathogenic ★★ same type
MTTP p.Gly49fs Pathogenic/Likely pathogenic ★★ same type
MTTP p.Ile650fs Pathogenic/Likely pathogenic ★★ same type
MTTP p.Leu125fs Pathogenic/Likely pathogenic ★★ same type
MTTP p.Phe399fs Pathogenic/Likely pathogenic ★★ same type

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-lys35fs (accessed [today's date]).

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