Is PEX16 p.Arg293Ser (c.877C>A) pathogenic?

PEX16 p.Arg293Ser (c.877C>A) is classified Uncertain significance in PEX16 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-23). AlphaMissense: likely benign (0.2013); Very rare (popmax 0.00178%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Arg293Ser (c.877C>A)?

PEX16 p.Arg293Ser (c.877C>A) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Arg293Ser (c.877C>A) in the general population?

PEX16 p.Arg293Ser (c.877C>A) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about PEX16 p.Arg293Ser (c.877C>A)?

AlphaMissense predicts likely benign (score 0.2013) — an in-silico prediction, not a clinical call.

PEX16 p.Arg293Ser

c.877C>A · rs544053792 · VCV855996

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2013 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
AlphaMissense	0.2013	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -8.71	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 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	23.7	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 0.00178% European (non-Finnish) · 21/1,179,996 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,613,996 alleles · very rare exomes 22/1,461,656 · genomes 1/152,340 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,190
Admixed American	0.00167%	60,030
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Arg293Ser
Coding: c.877C>A
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

peroxisome biogenesis disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX16 p.Arg293Cys 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-arg293ser (accessed [today's date]).

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