Is PEX12 p.Arg102Ser (c.306A>T) pathogenic?

PEX12 p.Arg102Ser (c.306A>T) is classified Uncertain significance in PEX12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.166); Ultra-rare (popmax 0.036%, afr); Associated with peroxisome biogenesis disorder 3A (Zellweger).

What condition is associated with PEX12 p.Arg102Ser (c.306A>T)?

PEX12 p.Arg102Ser (c.306A>T) is associated with peroxisome biogenesis disorder 3A (Zellweger) (ClinVar).

How common is PEX12 p.Arg102Ser (c.306A>T) in the general population?

PEX12 p.Arg102Ser (c.306A>T) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about PEX12 p.Arg102Ser (c.306A>T)?

AlphaMissense predicts likely benign (score 0.166) — an in-silico prediction, not a clinical call.

PEX12 p.Arg102Ser

c.306A>T · rs563487343 · VCV864735

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.166 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 3A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.166	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -4.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.099	phastCons 0.013
Regional constraint	o/e 0.86	unconstrained · MANE · 2,236 bp · p 0.0034 · regional, not allelic
Overall
CADD	9.965	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 0.036% African / African-American · 27/75,028 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00173% 28/1,614,114 alleles · ultra-rare exomes 14/1,461,870 · genomes 14/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,779
South Asian	0.0011%	91,078

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: PEX12
Protein: p.Arg102Ser
Coding: c.306A>T
MANE Select: NM_000286
dbSNP: rs563487343
Type: single nucleotide variant
Location: chr17:35577412 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.58

Full PEX12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 3A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX12 p.Arg102Thr Uncertain significance ★ ⚠ same residue
PEX12 p.Arg102fs Pathogenic ★ same residue
PEX12 c.126+1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX12 c.680+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg180Ter Pathogenic ★★ same condition
PEX12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln111Ter 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/pex12-p-arg102ser (accessed [today's date]).

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