Is PEX2 p.Cys184Phe (c.551G>T) pathogenic?

PEX2 p.Cys184Phe (c.551G>T) is classified Uncertain significance in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-13). AlphaMissense: likely benign (0.2292); Ultra-rare (popmax 0.0646%, eas).

How common is PEX2 p.Cys184Phe (c.551G>T) in the general population?

PEX2 p.Cys184Phe (c.551G>T) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

What do computational predictors say about PEX2 p.Cys184Phe (c.551G>T)?

AlphaMissense predicts likely benign (score 0.2292) — an in-silico prediction, not a clinical call.

PEX2 p.Cys184Phe

c.551G>T · rs1266603500 · VCV594546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2292 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2292	likely benign
REVEL	0.461	indeterminate
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	22.3	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 0.0646% East Asian · 29/44,886 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.00186% 30/1,613,782 alleles · ultra-rare exomes 28/1,461,620 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,548
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: PEX2
Protein: p.Cys184Phe
Coding: c.551G>T
MANE Select: NM_000318
dbSNP: rs1266603500
Type: single nucleotide variant
Location: chr8:76983628 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 184: a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a); a UniProt-annotated variant site (in)

Full PEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PEX2 p.Cys184Tyr Uncertain significance ★★ ⚠ same residue
PEX2 p.Cys184= Benign ★★ same residue
PEX2 p.Cys184Arg Benign ★★ same residue
PEX2 p.Cys184fs Pathogenic ★ same residue
PEX2 p.Cys184His Uncertain significance ★ same residue
PEX2 p.Cys184Leu Uncertain significance ★ same residue
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same type
PEX2 p.Arg119Ter 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/pex2-p-cys184phe (accessed [today's date]).

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