Is PEX10 p.Val222Phe (c.664G>T) pathogenic?

PEX10 p.Val222Phe (c.664G>T) is classified Uncertain significance in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-20). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.0011%, nfe); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Val222Phe (c.664G>T)?

PEX10 p.Val222Phe (c.664G>T) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Val222Phe (c.664G>T) in the general population?

PEX10 p.Val222Phe (c.664G>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about PEX10 p.Val222Phe (c.664G>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

PEX10 p.Val222Phe

c.664G>T · VCV3705279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -7.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.17	GERP -4
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	1.938	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0011% European (non-Finnish) · 13/1,178,852 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000807% 13/1,610,466 alleles · very rare exomes 12/1,458,222 · genomes 1/152,244 · 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: PEX10
Protein: p.Val222Phe
Coding: c.664G>T
MANE Select: NM_002617
Type: single nucleotide variant
Location: chr1:2406832 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81

Full PEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peroxisome biogenesis disorder, complementation group 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX10 p.Val222fs Pathogenic ★ same residue
PEX10 p.Val222Ala Uncertain significance ★ ⚠ same residue
PEX10 p.Val222Ile Uncertain significance ★ ⚠ same residue
PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+5G>A 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/pex10-p-val222phe (accessed [today's date]).

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