Is PEX6 p.Gln73= (c.219G>A) pathogenic?

PEX6 p.Gln73= (c.219G>A) is classified Conflicting classifications of pathogenicity in PEX6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-11). Ultra-rare (popmax 0.035%, afr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Gln73= (c.219G>A)?

PEX6 p.Gln73= (c.219G>A) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Gln73= (c.219G>A) in the general population?

PEX6 p.Gln73= (c.219G>A) is ultra-rare (popmax 0.035%, afr) (gnomAD).

PEX6 p.Gln73=

c.219G>A · rs191944205 · VCV594374

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, afr)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -0.71, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% African / African-American · 24/68,544 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00175% 26/1,489,202 alleles · ultra-rare exomes 14/1,336,988 · genomes 12/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.035%	2,856
Admixed American	0.00226%	44,266
Remaining individualsnot grpmax-eligible	0.00174%	57,596

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: PEX6
Protein: p.Gln73=
Coding: c.219G>A
MANE Select: NM_000287
dbSNP: rs191944205
Type: single nucleotide variant
Location: chr6:42978932 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.87

Full PEX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

PEX6 p.Gln73Ter Pathogenic ★ same residue
PEX6 c.1130+1G>A Likely pathogenic ★★ same condition
PEX6 c.1233+1G>A Likely pathogenic ★★ same condition
PEX6 c.1688+1G>A Pathogenic ★★ same condition
PEX6 c.1689-1G>A Likely pathogenic ★★ same condition
PEX6 c.1885-1G>A Likely pathogenic ★★ same condition
PEX6 c.1962-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX6 c.2094+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/pex6-p-gln73 (accessed [today's date]).

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