Is PEX14 p.Asp331Glu (c.993T>G) pathogenic?

PEX14 p.Asp331Glu (c.993T>G) is classified Conflicting classifications of pathogenicity in PEX14 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0756); Rare (popmax 0.264%, eas); Associated with peroxisome biogenesis disorder, complementation group K.

How common is PEX14 p.Asp331Glu (c.993T>G) in the general population?

PEX14 p.Asp331Glu (c.993T>G) is rare (popmax 0.264%, eas) (gnomAD).

What do computational predictors say about PEX14 p.Asp331Glu (c.993T>G)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

PEX14 p.Asp331Glu

Q: What condition is associated with PEX14 p.Asp331Glu (c.993T>G)?

PEX14 p.Asp331Glu (c.993T>G) is associated with peroxisome biogenesis disorder, complementation group K, peroxisome biogenesis disorder 13A (Zellweger) (ClinVar).

c.993T>G · rs79954820 · VCV291682

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.264%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder, complementation group K

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.40	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 -2.8
Regional constraint	o/e 0.90	unconstrained · MANE · 325 bp · p 0.21 · regional, not allelic
Overall
CADD	0.001	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 0.264% East Asian · 118/44,720 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.211%

Overall 0.0167% 268/1,607,500 alleles · rare exomes 246/1,455,984 · genomes 22/151,516 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.264%	379
Ashkenazi Jewishnot grpmax-eligible	0.234%	428
Remaining individualsnot grpmax-eligible	0.0289%	3,460
Admixed American	0.0201%	4,979
African / African-American	0.00804%	12,444
South Asian	0.00661%	15,127
European (non-Finnish)	0.00332%	30,130

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: PEX14
Protein: p.Asp331Glu
Coding: c.993T>G
MANE Select: NM_004565
dbSNP: rs79954820
Type: single nucleotide variant
Location: chr1:10629846 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.91 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 4 PDB
Residue 331: the 'disordered' region

Full PEX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: peroxisome biogenesis disorder 13A (Zellweger)

Similar variants

PEX14 p.Asp331Asn Uncertain significance ★ ⚠ same residue
PEX14 p.Asp331_Asp332insGluGluAsp Uncertain significance ★★ same residue
PEX14 c.36+6G>T Uncertain significance ★★ same condition
PEX14 p.Ala102Thr Uncertain significance ★★ ⚠ same condition
PEX14 p.Ala254Val Uncertain significance ★★ ⚠ same condition
PEX14 p.Ala370Ser Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg105Gln Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg139Leu 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/pex14-p-asp331glu (accessed [today's date]).

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