Is PEX6 p.Ala955= (c.2865C>T) pathogenic?

PEX6 p.Ala955= (c.2865C>T) is classified Likely benign in PEX6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). Very rare (popmax 0.00446%, eas); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ala955= (c.2865C>T)?

PEX6 p.Ala955= (c.2865C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Ala955= (c.2865C>T) in the general population?

PEX6 p.Ala955= (c.2865C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

PEX6 p.Ala955=

c.2865C>T · rs1407928755 · VCV1125969

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -10	GERP -3.4
Overall
CADD	0.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000744% 12/1,613,826 alleles · very rare exomes 12/1,461,498 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
Admixed American	0.00167%	60,018
Finnishnot grpmax-eligible	0.00157%	63,820
South Asian	0.0011%	91,076
European (non-Finnish)	0.000593%	168,570

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.Ala955=
Coding: c.2865C>T
MANE Select: NM_000287
dbSNP: rs1407928755
Type: single nucleotide variant
Location: chr6:42964413 (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-ala955 (accessed [today's date]).

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