Is PEX5 p.Ser417Phe (c.1250C>T) pathogenic?

PEX5 p.Ser417Phe (c.1250C>T) is classified Uncertain significance in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely pathogenic (0.7227); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX5 p.Ser417Phe (c.1250C>T)?

PEX5 p.Ser417Phe (c.1250C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PEX5 p.Ser417Phe (c.1250C>T) in the general population?

PEX5 p.Ser417Phe (c.1250C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about PEX5 p.Ser417Phe (c.1250C>T)?

AlphaMissense predicts likely pathogenic (score 0.7227) — an in-silico prediction, not a clinical call.

PEX5 p.Ser417Phe

c.1250C>T · rs769785732 · VCV3211511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7227	likely pathogenic
REVEL	0.746	pathogenic-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -0.28, phastCons 1
Overall
CADD	29.5	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 0.000593% European (non-Finnish) · 7/1,180,002 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,614,006 alleles · very rare exomes 6/1,461,820 · genomes 1/152,186 · 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: PEX5
Protein: p.Ser417Phe
Coding: c.1250C>T
MANE Select: NM_001351132
dbSNP: rs769785732
Type: single nucleotide variant
Location: chr12:7208525 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB

Full PEX5 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

Similar variants

PEX5 p.Ser417= Likely benign ★ same residue
PEX5 p.Ala240Pro Uncertain significance ★★ same condition
PEX5 p.Ala410Val Uncertain significance ★★ ⚠ same condition
PEX5 p.Ala625Val Uncertain significance ★★ ⚠ same condition
PEX5 p.Arg183Cys Uncertain significance ★★ ⚠ same condition
PEX5 p.Arg237Gln Uncertain significance ★★ ⚠ same condition
PEX5 p.Arg301Trp Uncertain significance ★★ ⚠ same condition
PEX5 p.Arg31Gln Uncertain significance ★★ ⚠ 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/pex5-p-ser417phe (accessed [today's date]).

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