Is PEX7 p.Asp304Val (c.911A>T) pathogenic?

PEX7 p.Asp304Val (c.911A>T) is classified Conflicting classifications of pathogenicity in PEX7 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-09). AlphaMissense: likely pathogenic (0.9787); Very rare (popmax 0.00667%, amr); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Asp304Val (c.911A>T)?

PEX7 p.Asp304Val (c.911A>T) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Asp304Val (c.911A>T) in the general population?

PEX7 p.Asp304Val (c.911A>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about PEX7 p.Asp304Val (c.911A>T)?

AlphaMissense predicts likely pathogenic (score 0.9787) — an in-silico prediction, not a clinical call.

PEX7 p.Asp304Val

c.911A>T · rs751429361 · VCV2197739

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.9787	likely pathogenic · top 8% in PEX7
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -4.27	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 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	28.5	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 0.00667% Admixed American · 4/59,982 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000435% 7/1,610,936 alleles · very rare exomes 7/1,458,712 · genomes 0/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
East Asian	0.00223%	44,790
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)	8.49e-05%	1,177,614

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.Asp304Val
Coding: c.911A>T
MANE Select: NM_000288
dbSNP: rs751429361
Type: single nucleotide variant
Location: chr6:136913465 (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

peroxisome biogenesis disorder 9B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp304val (accessed [today's date]).

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