Is PEX7 p.Ser164Pro (c.490T>C) pathogenic?

PEX7 p.Ser164Pro (c.490T>C) is classified Uncertain significance in PEX7 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-06). AlphaMissense: likely pathogenic (0.9769); Absent from gnomAD v4.1; Associated with rhizomelic chondrodysplasia punctata type 1.

What condition is associated with PEX7 p.Ser164Pro (c.490T>C)?

PEX7 p.Ser164Pro (c.490T>C) is associated with rhizomelic chondrodysplasia punctata type 1 (ClinVar).

How common is PEX7 p.Ser164Pro (c.490T>C) in the general population?

PEX7 p.Ser164Pro (c.490T>C) is absent from gnomAD v4.1 (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.Ser164Pro (c.490T>C)?

AlphaMissense predicts likely pathogenic (score 0.9769) — an in-silico prediction, not a clinical call.

PEX7 p.Ser164Pro

c.490T>C · rs62653607 · VCV551877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

rhizomelic chondrodysplasia punctata type 1

Computational evidence

Protein change
AlphaMissense	0.9769	likely pathogenic · top 8% in PEX7
REVEL	0.76	pathogenic-leaning
SaProt	LLR -14.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX7
Protein: p.Ser164Pro
Coding: c.490T>C
MANE Select: NM_000288
dbSNP: rs62653607
Type: single nucleotide variant
Location: chr6:136846145 (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

For Rhizomelic chondrodysplasia punctata (Orphanet):

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

Similar variants

PEX7 p.Ser164= Likely benign ★ same residue
PEX7 c.130+1G>A 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.634-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.748-2A>G Likely pathogenic ★★ same condition
PEX7 c.803+1G>A Likely pathogenic ★★ same condition
PEX7 c.903+1G>C 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-ser164pro (accessed [today's date]).

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