Is PEX7 p.Thr14Pro (c.40A>C) pathogenic?

PEX7 p.Thr14Pro (c.40A>C) is classified Pathogenic/Likely pathogenic in PEX7 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-10). AlphaMissense: likely benign (0.1817); Very rare (popmax 0.00158%, nfe); Associated with rhizomelic chondrodysplasia punctata.

What condition is associated with PEX7 p.Thr14Pro (c.40A>C)?

PEX7 p.Thr14Pro (c.40A>C) is associated with rhizomelic chondrodysplasia punctata, rhizomelic chondrodysplasia punctata type 1, peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Thr14Pro (c.40A>C) in the general population?

PEX7 p.Thr14Pro (c.40A>C) is very rare (popmax 0.00158%, nfe) (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.Thr14Pro (c.40A>C)?

AlphaMissense predicts likely benign (score 0.1817) — an in-silico prediction, not a clinical call.

PEX7 p.Thr14Pro

c.40A>C · rs61753233 · VCV7790

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00158%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

rhizomelic chondrodysplasia punctata

Computational evidence

Protein change
AlphaMissense	0.1817	likely benign ⚠ discordant with ClinVar
REVEL	0.611	indeterminate
SaProt	LLR -11.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	23.5	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 0.00158% European (non-Finnish) · 18/1,139,532 alleles

Filtering AF 0.000987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000814%

Overall 0.00119% 18/1,517,438 alleles · very rare exomes 18/1,365,516 · genomes 0/151,922 · 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.Thr14Pro
Coding: c.40A>C
MANE Select: NM_000288
dbSNP: rs61753233
Type: single nucleotide variant
Location: chr6:136822705 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.54
Residue 14: a UniProt-annotated variant site (in pbd9b)

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

Disease context

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

Also linked: rhizomelic chondrodysplasia punctata type 1 peroxisome biogenesis disorder 9B

For Rhizomelic chondrodysplasia punctata (Orphanet):

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

Similar variants

PEX7 p.Thr14Met Uncertain significance ★ ⚠ same residue
PEX7 p.Thr14= Likely benign ★ same residue
PEX7 p.Thr14_Pro15insLeuArgThr Uncertain significance ★ 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
PEX7 c.340-1G>T 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-thr14pro (accessed [today's date]).

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