Is PEX16 p.Arg5Trp (c.13C>T) pathogenic?

PEX16 p.Arg5Trp (c.13C>T) is classified Uncertain significance in PEX16 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-13). AlphaMissense: likely benign (0.331); Ultra-rare (popmax 0.0131%, sas); Associated with Inborn genetic diseases.

What condition is associated with PEX16 p.Arg5Trp (c.13C>T)?

PEX16 p.Arg5Trp (c.13C>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Arg5Trp (c.13C>T) in the general population?

PEX16 p.Arg5Trp (c.13C>T) is ultra-rare (popmax 0.0131%, sas) (gnomAD).

What do computational predictors say about PEX16 p.Arg5Trp (c.13C>T)?

AlphaMissense predicts likely benign (score 0.331) — an in-silico prediction, not a clinical call.

PEX16 p.Arg5Trp

c.13C>T · rs768102300 · VCV1494820

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.331 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0131%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.331	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -9.97	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 8.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,554 bp · p 0.075 · regional, not allelic
Overall
CADD	32.0	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 0.0131% South Asian · 11/84,118 alleles

Filtering AF 0.0073% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00561%

Overall 0.00104% 16/1,542,816 alleles · ultra-rare exomes 13/1,390,570 · genomes 3/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0131%	7,647
African / African-American	0.00684%	14,619

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: PEX16
Protein: p.Arg5Trp
Coding: c.13C>T
MANE Select: NM_004813
dbSNP: rs768102300
Type: single nucleotide variant
Location: chr11:45917799 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07

Full PEX16 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

Similar variants

PEX16 p.Arg5= Likely benign ★ same residue
PEX16 c.888-1G>C Likely pathogenic ★★ same condition
PEX16 p.Arg176Ter Pathogenic ★★ same condition
PEX16 p.Arg227Trp Likely pathogenic ★★ same condition
PEX16 p.Arg287Cys Pathogenic/Likely pathogenic ★★ same condition
PEX16 p.Arg287His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PEX16 c.225+3G>A Uncertain significance ★★ same condition
PEX16 p.Ala114Thr 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/pex16-p-arg5trp (accessed [today's date]).

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