Is PEX7 p.Pro316Ser (c.946C>T) pathogenic?

PEX7 p.Pro316Ser (c.946C>T) is classified Uncertain significance in PEX7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.5476); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX7 p.Pro316Ser (c.946C>T)?

PEX7 p.Pro316Ser (c.946C>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Pro316Ser (c.946C>T) in the general population?

PEX7 p.Pro316Ser (c.946C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about PEX7 p.Pro316Ser (c.946C>T)?

AlphaMissense predicts ambiguous (score 0.5476) — an in-silico prediction, not a clinical call.

PEX7 p.Pro316Ser

c.946C>T · rs746310299 · VCV1370514

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5476 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5476	ambiguous
REVEL	0.296	indeterminate
SaProt	LLR -3.57	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.8, 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 0.00102% European (non-Finnish) · 12/1,178,818 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00093% 15/1,612,176 alleles · very rare exomes 14/1,460,174 · genomes 1/152,002 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00314%	31,854
Remaining individualsnot grpmax-eligible	0.0016%	62,414
European (non-Finnish)grpmax	0.00102%	98,235

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro316Ser
Coding: c.946C>T
MANE Select: NM_000288
dbSNP: rs746310299
Type: single nucleotide variant
Location: chr6:136913500 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 9B

Similar variants

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
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

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-pro316ser (accessed [today's date]).

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