Is PEX7 p.Arg246Ter (c.735dup) pathogenic?

PEX7 p.Arg246Ter (c.735dup) is classified Likely pathogenic in PEX7 (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with rhizomelic chondrodysplasia punctata type 1.

What condition is associated with PEX7 p.Arg246Ter (c.735dup)?

PEX7 p.Arg246Ter (c.735dup) is associated with rhizomelic chondrodysplasia punctata type 1 (ClinVar).

How common is PEX7 p.Arg246Ter (c.735dup) in the general population?

PEX7 p.Arg246Ter (c.735dup) is no gnomAD frequency available for this variant (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

PEX7 p.Arg246Ter

c.735dup · rs1582760004 · VCV813367

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

rhizomelic chondrodysplasia punctata type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP 0.73, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX7
Protein: p.Arg246Ter
Coding: c.735dup
MANE Select: NM_000288
dbSNP: rs1582760004
Type: Duplication
Location: chr6:136869989 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PEX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

rhizomelic chondrodysplasia punctata type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PEX7 p.Arg246Lys Uncertain significance ★★ ⚠ same residue
PEX7 p.Leu70fs Likely pathogenic ★★ same condition
PEX7 c.130+48_130+53dup Benign ★★ same condition
PEX7 p.Leu213fs Likely pathogenic ★ same condition
PEX7 p.Ser87fs Likely pathogenic ★ same condition
PEX7 p.Arg246Gly Uncertain significance ★ ⚠ same residue
PEX7 p.Arg246Met Uncertain significance ★ ⚠ same residue
PEX7 p.Trp183fs 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/pex7-p-arg246ter (accessed [today's date]).

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