Is SLC39A4 p.Phe416fs (c.1247_1256del) pathogenic?

SLC39A4 p.Phe416fs (c.12471256del) is classified Likely pathogenic in SLC39A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). Associated with acrodermatitis enteropathica.

What condition is associated with SLC39A4 p.Phe416fs (c.1247_1256del)?

SLC39A4 p.Phe416fs (c.1247_1256del) is associated with acrodermatitis enteropathica (ClinVar).

How is Acrodermatitis enteropathica inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SLC39A4 p.Phe416fs

c.1247_1256del · VCV4816451

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

acrodermatitis enteropathica

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -2.2, phastCons 1

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

Variant & gene context

Gene: SLC39A4
Protein: p.Phe416fs
Coding: c.1247_1256del
MANE Select: NM_130849
Type: Deletion
Location: chr8:144413989 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.05

Full SLC39A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acrodermatitis enteropathica — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acrodermatitis enteropathica (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Denmark)

Similar variants

SLC39A4 c.1465_1474+4del Pathogenic/Likely pathogenic ★★ same condition
SLC39A4 p.Glu392fs Pathogenic/Likely pathogenic ★★ same condition
SLC39A4 p.Gly287_Val288insTer Pathogenic/Likely pathogenic ★★ same condition
SLC39A4 p.Leu410fs Pathogenic ★★ same condition
SLC39A4 p.Leu7fs Pathogenic/Likely pathogenic ★★ same condition
SLC39A4 p.Lys463fs Pathogenic/Likely pathogenic ★★ same condition
SLC39A4 p.Ser324fs Pathogenic ★★ same condition
SLC39A4 p.Val356fs Pathogenic/Likely pathogenic ★★ same condition

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/slc39a4-p-phe416fs (accessed [today's date]).

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