Is PEX1 p.Arg896Gln (c.2687G>A) pathogenic?

PEX1 p.Arg896Gln (c.2687G>A) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-05-30). AlphaMissense: likely benign (0.0807); Very rare (popmax 0.00446%, eas).

How common is PEX1 p.Arg896Gln (c.2687G>A) in the general population?

PEX1 p.Arg896Gln (c.2687G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about PEX1 p.Arg896Gln (c.2687G>A)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

PEX1 p.Arg896Gln

c.2687G>A · rs748798206 · VCV502332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.9, phastCons 0.66
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	21.4	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 0.00446% East Asian · 2/44,856 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00103% 15/1,460,986 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,428
African / African-American	0.004%	25,003
South Asian	0.0022%	45,528
European (non-Finnish)	0.000678%	147,407

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.Arg896Gln
Coding: c.2687G>A
MANE Select: NM_000466
dbSNP: rs748798206
Type: single nucleotide variant
Location: chr7:92499735 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 896: a UniProt-annotated variant site (in pbd1a)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PEX1 p.Arg896Ter Pathogenic/Likely pathogenic ★★ same residue
PEX1 p.Arg896Gly Uncertain significance ★ ⚠ same residue
PEX1 p.Arg896Leu Uncertain significance ★ ⚠ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same type
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.1483+1G>A Pathogenic ★★ same type

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-arg896gln (accessed [today's date]).

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