Is PEX6 p.Pro118Ser (c.352C>T) pathogenic?

PEX6 p.Pro118Ser (c.352C>T) is classified Uncertain significance in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely benign (0.0856); Ultra-rare (popmax 0.0221%, mid); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Pro118Ser (c.352C>T)?

PEX6 p.Pro118Ser (c.352C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Pro118Ser (c.352C>T) in the general population?

PEX6 p.Pro118Ser (c.352C>T) is ultra-rare (popmax 0.0221%, mid) (gnomAD).

What do computational predictors say about PEX6 p.Pro118Ser (c.352C>T)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

PEX6 p.Pro118Ser

c.352C>T · rs1040900085 · VCV1898467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0221%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.46, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.19 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0221% Middle Eastern · 1/4,526 alleles

Overall 0.00013% 2/1,533,754 alleles · ultra-rare exomes 1/1,381,682 · genomes 1/152,072 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0221%	4,526
African / African-American	0.00137%	72,952

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.Pro118Ser
Coding: c.352C>T
MANE Select: NM_000287
dbSNP: rs1040900085
Type: single nucleotide variant
Location: chr6:42978799 (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.Pro118= Likely benign 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
PEX6 c.2094+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-pro118ser (accessed [today's date]).

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