Is PEX6 p.Asp338= (c.1014C>T) pathogenic?

PEX6 p.Asp338= (c.1014C>T) is classified Conflicting classifications of pathogenicity in PEX6 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-22). Rare (popmax 0.104%, afr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Asp338= (c.1014C>T)?

PEX6 p.Asp338= (c.1014C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Asp338= (c.1014C>T) in the general population?

PEX6 p.Asp338= (c.1014C>T) is rare (popmax 0.104%, afr) (gnomAD).

PEX6 p.Asp338=

c.1014C>T · rs140806942 · VCV500942

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.104%, 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	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP -3, phastCons 1
Overall
CADD	7.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% African / African-American · 78/75,008 alleles

Filtering AF 0.0854% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0785%

Overall 0.00638% 103/1,613,948 alleles · rare exomes 50/1,461,734 · genomes 53/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.104%	962
Remaining individualsnot grpmax-eligible	0.0128%	7,812
Admixed American	0.0117%	8,572
East Asian	0.00891%	11,220
European (non-Finnish)	0.000509%	196,649

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.Asp338=
Coding: c.1014C>T
MANE Select: NM_000287
dbSNP: rs140806942
Type: single nucleotide variant
Location: chr6:42974907 (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.Asp338Gly Uncertain significance ★★ same residue
PEX6 p.Asp338Asn Uncertain significance ★ ⚠ 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

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-asp338 (accessed [today's date]).

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