Is DEF6 p.Arg339= (c.1017C>A) pathogenic?

DEF6 p.Arg339= (c.1017C>A) is classified Likely benign in DEF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). Absent from gnomAD v4.1.

How common is DEF6 p.Arg339= (c.1017C>A) in the general population?

DEF6 p.Arg339= (c.1017C>A) is absent from gnomAD v4.1 (gnomAD).

DEF6 p.Arg339=

c.1017C>A · rs2534189622 · VCV2036340

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 0.2	GERP -1.5, phastCons 0.97
Overall
CADD	12.91	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: DEF6
Protein: p.Arg339=
Coding: c.1017C>A
MANE Select: NM_022047
dbSNP: rs2534189622
Type: single nucleotide variant
Location: chr6:35318273 (GRCh38)
Gene constraint: LOEUF 0.61 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.91
Residue 339: a UniProt-annotated variant site (in imd87; protein not detected in homozygous patient t cells or when the mutant is expressed in a heterologous system); the 'disordered' region

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

Similar variants

DEF6 p.Arg339Cys Uncertain significance ★ ⚠ same residue
DEF6 p.Ala395Glu Uncertain significance ★★ ⚠ same type
DEF6 p.Ala617Val Uncertain significance ★★ ⚠ same type
DEF6 p.Arg104Pro Uncertain significance ★★ ⚠ same type
DEF6 p.Arg104Trp Uncertain significance ★★ ⚠ same type
DEF6 p.Arg192Cys Uncertain significance ★★ ⚠ same type
DEF6 p.Arg195Gln Uncertain significance ★★ ⚠ same type
DEF6 p.Arg349Leu 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/def6-p-arg339 (accessed [today's date]).

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