Is PEX1 p.Ala300Thr (c.898G>A) pathogenic?

PEX1 p.Ala300Thr (c.898G>A) is classified Likely benign in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely benign (0.0656); Very rare (popmax 0.00568%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX1 p.Ala300Thr (c.898G>A)?

PEX1 p.Ala300Thr (c.898G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PEX1 p.Ala300Thr (c.898G>A) in the general population?

PEX1 p.Ala300Thr (c.898G>A) is very rare (popmax 0.00568%, nfe) (gnomAD).

What do computational predictors say about PEX1 p.Ala300Thr (c.898G>A)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

PEX1 p.Ala300Thr

c.898G>A · VCV3417069

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -2.7
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	0.072	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 0.00568% European (non-Finnish) · 67/1,179,950 alleles

Filtering AF 0.00454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00421% 68/1,613,798 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,611
South Asian	0.0011%	91,092

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: PEX1
Protein: p.Ala300Thr
Coding: c.898G>A
MANE Select: NM_000466
Type: single nucleotide variant
Location: chr7:92517617 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

Full PEX1 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

PEX1 p.Ala300= Likely benign ★★ same residue
PEX1 p.Ala300Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX1 p.Ala300Val Uncertain significance ★ ⚠ same residue
PEX1 p.Ala272Thr Uncertain significance ★★ ⚠ same condition
PEX1 p.Arg633Gln Uncertain significance ★★ ⚠ same condition
PEX1 p.Asp1168Asn Uncertain significance ★★ ⚠ same condition
PEX1 p.Asp417Asn Uncertain significance ★★ ⚠ same condition
PEX1 p.Gln448Leu 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/pex1-p-ala300thr (accessed [today's date]).

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