Is TPP1 p.Arg339= (c.1017G>T) pathogenic?

TPP1 p.Arg339= (c.1017G>T) is classified Likely benign in TPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-19). Absent from gnomAD v4.1.

How common is TPP1 p.Arg339= (c.1017G>T) in the general population?

TPP1 p.Arg339= (c.1017G>T) is absent from gnomAD v4.1 (gnomAD).

TPP1 p.Arg339=

c.1017G>T · rs1490178326 · VCV1099233

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.41	GERP -2.1, phastCons 0.99
Overall
CADD	6.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TPP1
Protein: p.Arg339=
Coding: c.1017G>T
MANE Select: NM_000391
dbSNP: rs1490178326
Type: single nucleotide variant
Location: chr11:6616373 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.70 · 2 PDB
Residue 339: an α-helix; the peptidase s53 domain; a UniProt-annotated variant site (in cln2)

Full TPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TPP1 p.Arg339Trp Pathogenic/Likely pathogenic ★★ same residue
TPP1 p.Arg339Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TPP1 p.Arg339Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TPP1 c.1075+2T>C Pathogenic/Likely pathogenic ★★ same type
TPP1 c.1076-2A>G Pathogenic/Likely pathogenic ★★ same type
TPP1 c.1076-2A>T Pathogenic ★★ same type
TPP1 c.1146-1G>A Likely pathogenic ★★ same type
TPP1 c.1425+1G>A 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/tpp1-p-arg339 (accessed [today's date]).

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