Is PEX7 p.Val144fs (c.429del) pathogenic?

PEX7 p.Val144fs (c.429del) is classified Pathogenic/Likely pathogenic in PEX7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00134%, afr); Associated with rhizomelic chondrodysplasia punctata.

What condition is associated with PEX7 p.Val144fs (c.429del)?

PEX7 p.Val144fs (c.429del) is associated with rhizomelic chondrodysplasia punctata, rhizomelic chondrodysplasia punctata type 1, peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Val144fs (c.429del) in the general population?

PEX7 p.Val144fs (c.429del) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

PEX7 p.Val144fs

c.429del · rs61753248 · VCV554785

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

rhizomelic chondrodysplasia punctata

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 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP -1, phastCons 1
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,768 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00056% 9/1,607,116 alleles · very rare exomes 7/1,455,008 · genomes 2/152,108 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,548
African / African-Americangrpmax	0.00134%	74,768
European (non-Finnish)	0.000596%	167,701

Ashkenazi Jewish 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: PEX7
Protein: p.Val144fs
Coding: c.429del
MANE Select: NM_000288
dbSNP: rs61753248
Type: Deletion
Location: chr6:136846084 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhizomelic chondrodysplasia punctata type 1 peroxisome biogenesis disorder 9B

For Rhizomelic chondrodysplasia punctata (Orphanet):

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

Similar variants

PEX7 c.116_130+20del Likely pathogenic ★★ same condition
PEX7 c.363_526+230del Likely pathogenic ★★ same condition
PEX7 p.Glu211fs Likely pathogenic ★★ same condition
PEX7 p.Phe61fs Pathogenic/Likely pathogenic ★★ same condition
PEX7 p.Phe71fs Pathogenic ★★ same condition
PEX7 p.Ser173fs Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.747+20_747+24del Benign ★★ same condition
PEX7 c.748-5del Benign ★★ 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-val144fs (accessed [today's date]).

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