Is MTTP p.Arg409Ile (c.1226_1227delinsTT) pathogenic?

MTTP p.Arg409Ile (c.12261227delinsTT) is classified Uncertain significance in MTTP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-18). No gnomAD frequency available for this variant.

How common is MTTP p.Arg409Ile (c.1226_1227delinsTT) in the general population?

MTTP p.Arg409Ile (c.1226_1227delinsTT) is no gnomAD frequency available for this variant (gnomAD).

MTTP p.Arg409Ile

c.1226_1227delinsTT · rs2110224707 · VCV1412047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP -1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 48 kb · p 0.00018 · regional, not allelic

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.Arg409Ile
Coding: c.1226_1227delinsTT
MANE Select: NM_001386140
dbSNP: rs2110224707
Type: Indel
Location: chr4:99600723 (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 409: the vitellogenin domain; an α-helix

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

Similar variants

MTTP p.Gly444Asp Uncertain significance ★★ same type
MTTP p.Ala410fs Pathogenic ★ same type
MTTP p.Ala758fs Likely pathogenic ★ same type
MTTP p.Asn237delinsArgCysValTer Likely pathogenic ★ same type
MTTP p.Asn685fs Likely pathogenic ★ same type
MTTP p.Gly163fs Likely pathogenic ★ same type
MTTP p.Phe767fs Likely pathogenic ★ same type
MTTP p.Thr245fs 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-arg409ile (accessed [today's date]).

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