Is PEX16 p.Arg293Cys (c.877C>T) pathogenic?

PEX16 p.Arg293Cys (c.877C>T) is classified Uncertain significance in PEX16 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-11). AlphaMissense: likely benign (0.1311); Ultra-rare (popmax 0.0512%, eas); Associated with Inborn genetic diseases.

What condition is associated with PEX16 p.Arg293Cys (c.877C>T)?

PEX16 p.Arg293Cys (c.877C>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 8A (Zellweger), peroxisome biogenesis disorder 8B (ClinVar).

How common is PEX16 p.Arg293Cys (c.877C>T) in the general population?

PEX16 p.Arg293Cys (c.877C>T) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

What do computational predictors say about PEX16 p.Arg293Cys (c.877C>T)?

AlphaMissense predicts likely benign (score 0.1311) — an in-silico prediction, not a clinical call.

PEX16 p.Arg293Cys

c.877C>T · rs544053792 · VCV282806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1311 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1311	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -10.90	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,554 bp · p 0.075 · regional, not allelic
Overall
CADD	29.1	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 0.0512% East Asian · 23/44,880 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.025% 404/1,613,996 alleles · ultra-rare exomes 380/1,461,656 · genomes 24/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,951
Remaining individualsnot grpmax-eligible	0.0336%	2,976
European (non-Finnish)	0.0292%	3,430
Middle Eastern	0.0165%	6,062
African / African-American	0.00933%	10,722
Finnishnot grpmax-eligible	0.00626%	15,967
South Asian	0.00439%	22,772

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.Arg293Cys
Coding: c.877C>T
MANE Select: NM_004813
dbSNP: rs544053792
Type: single nucleotide variant
Location: chr11:45913829 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07
Residue 293: the 'interaction with pex19' region

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 8A (Zellweger)peroxisome biogenesis disorder 8B peroxisome biogenesis disorder

Similar variants

PEX16 p.Arg293Ser Uncertain significance ★★ ⚠ same residue
PEX16 p.Arg293His Uncertain significance ★ ⚠ 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

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-arg293cys (accessed [today's date]).

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