Is DLX5 p.Pro280fs (c.839del) pathogenic?

DLX5 p.Pro280fs (c.839del) is classified Uncertain significance in DLX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). Associated with split hand-foot malformation 1.

What condition is associated with DLX5 p.Pro280fs (c.839del)?

DLX5 p.Pro280fs (c.839del) is associated with split hand-foot malformation 1 (ClinVar).

DLX5 p.Pro280fs

c.839del · VCV3370334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

split hand-foot malformation 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -1.8, phastCons 0.99

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

Variant & gene context

Gene: DLX5
Protein: p.Pro280fs
Coding: c.839del
MANE Select: NM_005221
Type: Deletion
Location: chr7:97020767 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 61.56 · 2 PDB
Residue 280: the 'disordered' region

Full DLX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

split hand-foot malformation 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLX5 p.Leu170Pro Likely pathogenic ★ same condition
DLX5 p.Tyr161His Likely pathogenic ★ same condition
DLX5 p.Ser190Phe Uncertain significance ★ ⚠ same condition
DLX5 p.Ter290Glu Uncertain significance ★ same condition
DLX5 p.Glu39Ter Pathogenic same condition
DLX5 c.355+11del Benign/Likely benign ★★ same type
DLX5 p.Ser146fs Pathogenic ★ same type
DLX5 p.Gly53fs 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/dlx5-p-pro280fs (accessed [today's date]).

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