Is PEX7 p.His39= (c.117C>T) pathogenic?

PEX7 p.His39= (c.117C>T) is classified Likely benign in PEX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). Ultra-rare (popmax 0.0234%, sas); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.His39= (c.117C>T)?

PEX7 p.His39= (c.117C>T) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.His39= (c.117C>T) in the general population?

PEX7 p.His39= (c.117C>T) is ultra-rare (popmax 0.0234%, sas) (gnomAD).

PEX7 p.His39=

c.117C>T · rs779353296 · VCV1157805

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0234%, sas)

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -1, phastCons 0.99
Overall
CADD	12.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0234% South Asian · 13/55,460 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00169% 23/1,357,744 alleles · ultra-rare exomes 19/1,205,802 · genomes 4/151,942 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0234%	4,266
Remaining individualsnot grpmax-eligible	0.00195%	51,250
European (non-Finnish)	0.000849%	117,740

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: PEX7
Protein: p.His39=
Coding: c.117C>T
MANE Select: NM_000288
dbSNP: rs779353296
Type: single nucleotide variant
Location: chr6:136822782 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PEX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 9B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX7 p.His39Gln Uncertain significance ★★ ⚠ same residue
PEX7 p.His39Arg Uncertain significance ★ same residue
PEX7 p.His39Asn Uncertain significance ★ ⚠ same residue
PEX7 p.His39Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX7 c.130+1G>A Pathogenic ★★ same condition
PEX7 c.131-1G>A Likely pathogenic ★★ same condition
PEX7 c.188+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.188+1G>C Pathogenic/Likely pathogenic ★★ 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/pex7-p-his39 (accessed [today's date]).

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