Is PEX6 p.Ser417= (c.1251C>T) pathogenic?

PEX6 p.Ser417= (c.1251C>T) is classified Likely benign in PEX6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). Very rare (popmax 0.00267%, afr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ser417= (c.1251C>T)?

PEX6 p.Ser417= (c.1251C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Ser417= (c.1251C>T) in the general population?

PEX6 p.Ser417= (c.1251C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

PEX6 p.Ser417=

c.1251C>T · rs995542635 · VCV1094482

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

peroxisome biogenesis disorder

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	GERP 1.4, phastCons 1
Overall
CADD	9.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,824 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,756 alleles · very rare exomes 3/1,461,692 · genomes 1/152,064 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,412
Remaining individualsnot grpmax-eligible	0.0016%	62,462
South Asian	0.0011%	91,072

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.Ser417=
Coding: c.1251C>T
MANE Select: NM_000287
dbSNP: rs995542635
Type: single nucleotide variant
Location: chr6:42969784 (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 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
PEX6 c.2095-2A>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/pex6-p-ser417 (accessed [today's date]).

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