Is PEX2 p.Phe157Val (c.469T>G) pathogenic?

PEX2 p.Phe157Val (c.469T>G) is classified Uncertain significance in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-14). AlphaMissense: likely pathogenic (0.8231); Very rare (popmax 0.00267%, afr).

How common is PEX2 p.Phe157Val (c.469T>G) in the general population?

PEX2 p.Phe157Val (c.469T>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PEX2 p.Phe157Val (c.469T>G)?

AlphaMissense predicts likely pathogenic (score 0.8231) — an in-silico prediction, not a clinical call.

PEX2 p.Phe157Val

c.469T>G · VCV4900930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8231	likely pathogenic · top 7% in PEX2
REVEL	0.97	strongly pathogenic-leaning
SaProt	LLR -15.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,994 alleles · very rare exomes 1/1,461,788 · genomes 1/152,206 · 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: PEX2
Protein: p.Phe157Val
Coding: c.469T>G
MANE Select: NM_000318
Type: single nucleotide variant
Location: chr8:76983710 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 157: a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a)

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

Similar variants

PEX2 p.Phe157Cys Uncertain significance ⚠ same residue
PEX2 p.Phe157fs Pathogenic ★ same residue
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same type
PEX2 p.Arg119Ter Pathogenic ★★ same type
PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same type
PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same type
PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same type
PEX2 p.Gln96Ter 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-phe157val (accessed [today's date]).

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