Is PEX12 p.Arg151Cys (c.451C>T) pathogenic?

PEX12 p.Arg151Cys (c.451C>T) is classified Conflicting classifications of pathogenicity in PEX12 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1005); Rare (popmax 0.292%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX12 p.Arg151Cys (c.451C>T)?

PEX12 p.Arg151Cys (c.451C>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 3A (Zellweger) (ClinVar).

How common is PEX12 p.Arg151Cys (c.451C>T) in the general population?

PEX12 p.Arg151Cys (c.451C>T) is rare (popmax 0.292%, nfe) (gnomAD).

What do computational predictors say about PEX12 p.Arg151Cys (c.451C>T)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

PEX12 p.Arg151Cys

c.451C>T · rs138731505 · VCV92774

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.292%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,236 bp · p 0.0034 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.292% European (non-Finnish) · 3,447/1,179,990 alleles

Filtering AF 0.284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.281%

Overall 0.237% 3,828/1,614,090 alleles · rare exomes 3,565/1,461,862 · genomes 263/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.292%	342
Remaining individualsnot grpmax-eligible	0.195%	512
Admixed American	0.173%	577
Finnishnot grpmax-eligible	0.147%	681
African / African-American	0.0627%	1,596
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,922
South Asian	0.00769%	13,011

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.Arg151Cys
Coding: c.451C>T
MANE Select: NM_000286
dbSNP: rs138731505
Type: single nucleotide variant
Location: chr17:35577267 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 3A (Zellweger)

Similar variants

PEX12 p.Arg151His Conflicting classifications of pathogenicity ★ ⚠ 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
PEX12 p.Gln112Ter 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-arg151cys (accessed [today's date]).

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