Is DPP6 p.Pro53fs (c.157_184del) pathogenic?

DPP6 p.Pro53fs (c.157184del) is classified Conflicting classifications of pathogenicity in DPP6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-12-21). Very rare (popmax 0.00497%, amr).

How common is DPP6 p.Pro53fs (c.157_184del) in the general population?

DPP6 p.Pro53fs (c.157_184del) is very rare (popmax 0.00497%, amr) (gnomAD).

DPP6 p.Pro53fs

c.157_184del · rs2129062565 · VCV1677676

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00497%, amr)

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 1 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.89	GERP -4.3, phastCons 0.009
Region caveats
Repeat context	tandem	(GGC)n simple repeat, segmental duplication · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00497% Admixed American · 1/20,120 alleles

Overall 0.000269% 3/1,114,996 alleles · very rare exomes 3/968,078 · genomes 0/146,918 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00497%	20,120
Finnishnot grpmax-eligible	0.00464%	21,546
European (non-Finnish)	0.00011%	912,642

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: DPP6
Protein: p.Pro53fs
Coding: c.157_184del
MANE Select: NM_130797
dbSNP: rs2129062565
Type: Deletion
Location: chr7:154052967 (GRCh38)
Gene constraint: LOEUF 0.751 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 87.41 · 8 PDB
Residue 53: the 'disordered' region

Full DPP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPP6 c.627+20964_627+20966del Uncertain significance ★ same type
DPP6 p.Asp865fs Uncertain significance ★ same type
DPP6 c.1136+40del Benign ★ same type
DPP6 c.1261-48_1261-40del Benign ★ same type
DPP6 c.243+13del Benign ★ same type
DPP6 c.51+164380_51+164383del Benign ★ same type
DPP6 c.-88del Benign ★ same type
DPP6 c.49_51+7del Uncertain significance 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/dpp6-p-pro53fs (accessed [today's date]).

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