Is PEX7 p.His39Pro (c.116A>C) pathogenic?

PEX7 p.His39Pro (c.116A>C) is classified Conflicting classifications of pathogenicity in PEX7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-10). AlphaMissense: likely pathogenic (0.8406); Very rare (popmax 0.00152%, afr); Associated with rhizomelic chondrodysplasia punctata type 1.

What condition is associated with PEX7 p.His39Pro (c.116A>C)?

PEX7 p.His39Pro (c.116A>C) is associated with rhizomelic chondrodysplasia punctata type 1, peroxisome biogenesis disorder 9B, rhizomelic chondrodysplasia punctata (ClinVar).

How common is PEX7 p.His39Pro (c.116A>C) in the general population?

PEX7 p.His39Pro (c.116A>C) is very rare (popmax 0.00152%, afr) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PEX7 p.His39Pro (c.116A>C)?

AlphaMissense predicts likely pathogenic (score 0.8406) — an in-silico prediction, not a clinical call.

PEX7 p.His39Pro

c.116A>C · rs61753237 · VCV813362

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8406 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00152%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

rhizomelic chondrodysplasia punctata type 1

Computational evidence

Protein change
AlphaMissense	0.8406	likely pathogenic
REVEL	0.689	pathogenic-leaning
SaProt	LLR -12.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	26.5	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 0.00152% African / African-American · 1/65,666 alleles

Overall 7.36e-05% 1/1,358,756 alleles · very rare exomes 1/1,206,858 · genomes 0/151,898 · joint denominator

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.His39Pro
Coding: c.116A>C
MANE Select: NM_000288
dbSNP: rs61753237
Type: single nucleotide variant
Location: chr6:136822781 (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

rhizomelic chondrodysplasia punctata type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 9B rhizomelic chondrodysplasia punctata

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

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.His39= Likely benign ★ 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-his39pro (accessed [today's date]).

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