Is PEX16 p.Asp253= (c.759C>T) pathogenic?

PEX16 p.Asp253= (c.759C>T) is classified Likely benign in PEX16 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0165%, mid); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Asp253= (c.759C>T)?

PEX16 p.Asp253= (c.759C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Asp253= (c.759C>T) in the general population?

PEX16 p.Asp253= (c.759C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PEX16 p.Asp253=

c.759C>T · rs774788367 · VCV1158805

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.1	GERP -4.4
Overall
CADD	1.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.000503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000368%

Overall 0.00125% 20/1,601,158 alleles · ultra-rare exomes 17/1,449,348 · genomes 3/151,810 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,066
Remaining individualsnot grpmax-eligible	0.00323%	30,964
African / African-American	0.00269%	37,215
East Asian	0.00227%	43,990
South Asian	0.00223%	44,786
Admixed American	0.00172%	58,158
European (non-Finnish)	0.000937%	106,710

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.Asp253=
Coding: c.759C>T
MANE Select: NM_004813
dbSNP: rs774788367
Type: single nucleotide variant
Location: chr11:45914139 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07
Residue 253: 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.Asp253Val 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
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-asp253 (accessed [today's date]).

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