Is DEF6 p.Asp60del (c.171TGA[2]) pathogenic?

DEF6 p.Asp60del (c.171TGA[2]) is classified Uncertain significance in DEF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). Very rare (popmax 0.000169%, nfe).

How common is DEF6 p.Asp60del (c.171TGA[2]) in the general population?

DEF6 p.Asp60del (c.171TGA[2]) is very rare (popmax 0.000169%, nfe) (gnomAD).

DEF6 p.Asp60del

c.171TGA[2] · rs2534179159 · VCV1999545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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 0.052	GERP -3.8, phastCons 0.11

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,952 alleles

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

Overall 0.000205% 3/1,461,872 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,016
European (non-Finnish)grpmax	0.000169%	589,977

Finnish 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: DEF6
Protein: p.Asp60del
Coding: c.171TGA[2]
MANE Select: NM_022047
dbSNP: rs2534179159
Type: Microsatellite
Location: chr6:35309742 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91

Full DEF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DEF6 p.Asp60Asn Uncertain significance ★ same residue
DEF6 p.Asp60= Likely benign ★ same residue
DEF6 p.332QRE[1] Uncertain significance ★ same type
DEF6 p.Glu337_Arg338insGlnArgGlu Uncertain significance ★ same type
DEF6 p.Glu383del Uncertain significance ★ same type
DEF6 p.Glu383dup Uncertain significance ★ same type
DEF6 c.97-11_97-7del Likely benign ★ 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/def6-p-asp60del (accessed [today's date]).

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