Is PEX13 p.Ser67Arg (c.199A>C) pathogenic?

PEX13 p.Ser67Arg (c.199A>C) is classified Uncertain significance in PEX13 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-21). AlphaMissense: ambiguous (0.3996); Very rare (popmax 0.00373%, nfe); Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Ser67Arg (c.199A>C)?

PEX13 p.Ser67Arg (c.199A>C) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Ser67Arg (c.199A>C) in the general population?

PEX13 p.Ser67Arg (c.199A>C) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about PEX13 p.Ser67Arg (c.199A>C)?

AlphaMissense predicts ambiguous (score 0.3996) — an in-silico prediction, not a clinical call.

PEX13 p.Ser67Arg

c.199A>C · rs752073595 · VCV502033

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.3996	ambiguous
REVEL	0.194	benign-leaning
SaProt	LLR -8.16	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 31 kb · p 0.0078 · regional, not allelic
Overall
CADD	18.06	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 0.00373% European (non-Finnish) · 44/1,179,982 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.0031% 50/1,614,034 alleles · very rare exomes 46/1,461,818 · genomes 4/152,216 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00468%	21,348
European (non-Finnish)grpmax	0.00373%	26,818

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PEX13
Protein: p.Ser67Arg
Coding: c.199A>C
MANE Select: NM_002618
dbSNP: rs752073595
Type: single nucleotide variant
Location: chr2:61031525 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB
Residue 67: the 'disordered' region

Full PEX13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 11A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX13 p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg226Ter Pathogenic ★★ same condition
PEX13 p.Gln131Ter Pathogenic ★★ same condition
PEX13 p.Glu123Ter Pathogenic ★★ same condition
PEX13 p.Tyr155Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 c.913+3A>G Uncertain significance ★★ same condition
PEX13 p.Ala302Gly 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/pex13-p-ser67arg (accessed [today's date]).

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