Is PEX12 p.Pro285Ser (c.853C>T) pathogenic?

PEX12 p.Pro285Ser (c.853C>T) is classified Likely pathogenic in PEX12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-03). AlphaMissense: likely pathogenic (0.8129); Very rare (popmax 6.2e-05%).

How common is PEX12 p.Pro285Ser (c.853C>T) in the general population?

PEX12 p.Pro285Ser (c.853C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PEX12 p.Pro285Ser (c.853C>T)?

AlphaMissense predicts likely pathogenic (score 0.8129) — an in-silico prediction, not a clinical call.

PEX12 p.Pro285Ser

c.853C>T · rs2142229072 · VCV1319465

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8129 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8129	likely pathogenic ✓ concordant with ClinVar
REVEL	0.681	pathogenic-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,236 bp · p 0.0034 · regional, not allelic
Overall
CADD	26.4	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 6.2e-05%

Overall 6.2e-05% 1/1,614,120 alleles · very rare exomes 1/1,461,806 · genomes 0/152,314 · joint denominator

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.Pro285Ser
Coding: c.853C>T
MANE Select: NM_000286
dbSNP: rs2142229072
Type: single nucleotide variant
Location: chr17:35576009 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.58
Residue 285: a UniProt-annotated variant site (in pbd3a)

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

Similar variants

PEX12 c.126+1G>T Pathogenic/Likely pathogenic ★★ same type
PEX12 c.680+1G>A Pathogenic/Likely pathogenic ★★ same type
PEX12 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
PEX12 p.Arg180Ter Pathogenic ★★ same type
PEX12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same type
PEX12 p.Gln111Ter Pathogenic/Likely pathogenic ★★ same type
PEX12 p.Gln112Ter Pathogenic/Likely pathogenic ★★ same type
PEX12 p.Gln209Ter Pathogenic ★★ same type

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-pro285ser (accessed [today's date]).

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