Is PEX6 p.Arg812= (c.2436G>A) pathogenic?

PEX6 p.Arg812= (c.2436G>A) is classified Benign/Likely benign in PEX6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Rare (popmax 0.573%, afr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Arg812= (c.2436G>A)?

PEX6 p.Arg812= (c.2436G>A) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Arg812= (c.2436G>A) in the general population?

PEX6 p.Arg812= (c.2436G>A) is rare (popmax 0.573%, afr) (gnomAD).

PEX6 p.Arg812=

c.2436G>A · rs61732156 · VCV194166

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.573%, afr)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.568	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -2
Overall
CADD	8.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.573% African / African-American · 430/75,032 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.511%

Overall 0.0304% 491/1,614,138 alleles · rare exomes 239/1,461,828 · genomes 252/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.573%	174
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Admixed American	0.025%	4,002
European (non-Finnish)	0.000847%	118,000

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.Arg812=
Coding: c.2436G>A
MANE Select: NM_000287
dbSNP: rs61732156
Type: single nucleotide variant
Location: chr6:42965716 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.87
Residue 812: a UniProt-annotated variant site (in pbd4a); a UniProt-annotated variant site (in pbd4a; atypical)

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.Arg812Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX6 p.Arg812fs Pathogenic ★ same residue
PEX6 p.Arg812Gln Likely 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

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-arg812 (accessed [today's date]).

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