Is PEX10 p.Ser256Pro (c.766T>C) pathogenic?

PEX10 p.Ser256Pro (c.766T>C) is classified Uncertain significance in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.0729); Very rare (popmax 0.00442%, sas); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Ser256Pro (c.766T>C)?

PEX10 p.Ser256Pro (c.766T>C) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Ser256Pro (c.766T>C) in the general population?

PEX10 p.Ser256Pro (c.766T>C) is very rare (popmax 0.00442%, sas) (gnomAD).

What do computational predictors say about PEX10 p.Ser256Pro (c.766T>C)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

PEX10 p.Ser256Pro

c.766T>C · VCV4737514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00442%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 0.091, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	12.49	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 0.00442% South Asian · 4/90,404 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000896%

Overall 0.000311% 5/1,608,538 alleles · very rare exomes 5/1,456,234 · genomes 0/152,304 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00442%	22,601
European (non-Finnish)	8.49e-05%	1,178,137

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: PEX10
Protein: p.Ser256Pro
Coding: c.766T>C
MANE Select: NM_002617
Type: single nucleotide variant
Location: chr1:2406730 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 256: a UniProt-annotated variant site (in pbd6b and pbd6a)

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

Disease context

Peroxisome biogenesis disorder, complementation group 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX10 p.Ser256Thr Uncertain significance ★ ⚠ same residue
PEX10 p.Ser256= Likely benign ★ same residue
PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+5G>A Uncertain significance ★★ same condition
PEX10 p.Ala150Val Uncertain significance ★★ ⚠ 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-ser256pro (accessed [today's date]).

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