Is PEX6 p.Pro177fs (c.530del) pathogenic?

PEX6 p.Pro177fs (c.530del) is classified Pathogenic/Likely pathogenic in PEX6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-12). Very rare (popmax 0.00017%, nfe); Associated with PEX6-related disorder.

What condition is associated with PEX6 p.Pro177fs (c.530del)?

PEX6 p.Pro177fs (c.530del) is associated with PEX6-related disorder, peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Pro177fs (c.530del) in the general population?

PEX6 p.Pro177fs (c.530del) is very rare (popmax 0.00017%, nfe) (gnomAD).

PEX6 p.Pro177fs

c.530del · rs61753213 · VCV2734863

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

PEX6-related disorder

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 1 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.6	GERP -3.2
Overall
CADD	26.5	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 0.00017% European (non-Finnish) · 2/1,175,748 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00163% 26/1,597,382 alleles · very rare exomes 20/1,445,704 · genomes 6/151,678 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0406%	2,462
Remaining individualsnot grpmax-eligible	0.00161%	62,032
European (non-Finnish)grpmax	0.00017%	587,876

Finnish 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: PEX6
Protein: p.Pro177fs
Coding: c.530del
MANE Select: NM_000287
dbSNP: rs61753213
Type: Deletion
Location: chr6:42978621 (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

PEX6-related disorder

Also linked: peroxisome biogenesis disorder

Similar variants

PEX6 c.1368-2del Likely pathogenic ★★ same condition
PEX6 p.Arg343fs Pathogenic/Likely pathogenic ★★ same condition
PEX6 p.Asn233fs Pathogenic/Likely pathogenic ★★ same condition
PEX6 p.Asp268fs Pathogenic ★★ same condition
PEX6 p.Asp305fs Pathogenic/Likely pathogenic ★★ same condition
PEX6 p.Cys564fs Pathogenic/Likely pathogenic ★★ same condition
PEX6 p.Glu304fs Pathogenic/Likely pathogenic ★★ same condition
PEX6 p.Glu508fs 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-pro177fs (accessed [today's date]).

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