Is PEX10 p.Cys276Ser (c.827G>C) pathogenic?

PEX10 p.Cys276Ser (c.827G>C) is classified Pathogenic in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.9789); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 6A (Zellweger).

What condition is associated with PEX10 p.Cys276Ser (c.827G>C)?

PEX10 p.Cys276Ser (c.827G>C) is associated with peroxisome biogenesis disorder 6A (Zellweger) (ClinVar).

How common is PEX10 p.Cys276Ser (c.827G>C) in the general population?

PEX10 p.Cys276Ser (c.827G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX10 p.Cys276Ser (c.827G>C)?

AlphaMissense predicts likely pathogenic (score 0.9789) — an in-silico prediction, not a clinical call.

PEX10 p.Cys276Ser

c.827G>C · rs1414973726 · VCV1686018

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9789 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 6A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.9789	likely pathogenic ✓ concordant with ClinVar · top 1% in PEX10
REVEL	0.956	strongly pathogenic-leaning
SaProt	LLR -11.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX10
Protein: p.Cys276Ser
Coding: c.827G>C
MANE Select: NM_002617
dbSNP: rs1414973726
Type: single nucleotide variant
Location: chr1:2406569 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 276: a binding site; a UniProt-annotated variant site (in pbd6b and pbd6a); a UniProt-annotated variant site (in pbd6b)

Full PEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 6A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX10 p.Cys276Phe Likely pathogenic ★ same residue
PEX10 p.Cys276= Likely benign ★ same residue
PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.600+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 c.776+2T>C Likely pathogenic ★★ same condition
PEX10 c.777-1G>A Likely pathogenic ★★ same condition
PEX10 c.912+1G>C 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/pex10-p-cys276ser (accessed [today's date]).

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