Is PEX7 p.Thr281= (c.843A>G) pathogenic?

PEX7 p.Thr281= (c.843A>G) is classified Conflicting classifications of pathogenicity in PEX7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-04). Very rare (popmax 0.00221%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX7 p.Thr281= (c.843A>G)?

PEX7 p.Thr281= (c.843A>G) is associated with Inborn genetic diseases, rhizomelic chondrodysplasia punctata type 1, peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Thr281= (c.843A>G) in the general population?

PEX7 p.Thr281= (c.843A>G) is very rare (popmax 0.00221%, nfe) (gnomAD).

PEX7 p.Thr281=

c.843A>G · rs767903764 · VCV593499

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Conditions

Inborn genetic diseases

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 2.2	GERP 0.7, phastCons 1
Overall
CADD	8.821	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,178,786 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,612,648 alleles · very rare exomes 25/1,460,458 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00221%	45,338
Remaining individualsnot grpmax-eligible	0.0016%	62,438

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.Thr281=
Coding: c.843A>G
MANE Select: NM_000288
dbSNP: rs767903764
Type: single nucleotide variant
Location: chr6:136898181 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

PEX7 c.130+1G>A Pathogenic ★★ same condition
PEX7 c.131-1G>A Likely pathogenic ★★ same condition
PEX7 c.188+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.188+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.340-1G>T Likely pathogenic ★★ same condition
PEX7 c.634-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.748-2A>G Likely pathogenic ★★ same condition
PEX7 c.803+1G>A 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-thr281 (accessed [today's date]).

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