Is PEX7 p.Ala43= (c.129G>C) pathogenic?

PEX7 p.Ala43= (c.129G>C) is classified Uncertain significance in PEX7 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-28). Very rare (popmax 0.00309%, afr); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Ala43= (c.129G>C)?

PEX7 p.Ala43= (c.129G>C) is associated with peroxisome biogenesis disorder 9B, rhizomelic chondrodysplasia punctata type 1, adult Refsum disease (ClinVar).

How common is PEX7 p.Ala43= (c.129G>C) in the general population?

PEX7 p.Ala43= (c.129G>C) is very rare (popmax 0.00309%, afr) (gnomAD).

PEX7 p.Ala43=

c.129G>C · rs1256466654 · VCV1010243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00309%, afr)

Conditions

peroxisome biogenesis disorder 9B

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 3.1	GERP 0.6, phastCons 1
Overall
CADD	17.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00309% African / African-American · 2/64,792 alleles

Filtering AF 0.000512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000295%

Overall 0.000911% 12/1,317,486 alleles · very rare exomes 10/1,165,830 · genomes 2/151,656 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00309%	32,396
Remaining individualsnot grpmax-eligible	0.00202%	49,426
European (non-Finnish)	0.000866%	115,459

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.Ala43=
Coding: c.129G>C
MANE Select: NM_000288
dbSNP: rs1256466654
Type: single nucleotide variant
Location: chr6:136822794 (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

peroxisome biogenesis disorder 9B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhizomelic chondrodysplasia punctata type 1 adult Refsum disease rhizomelic chondrodysplasia punctata

Similar variants

PEX7 p.Ala43Val Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala43 (accessed [today's date]).

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