Is PEX1 p.Cys103Arg (c.307T>C) pathogenic?

PEX1 p.Cys103Arg (c.307T>C) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.9438); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with PEX1 p.Cys103Arg (c.307T>C)?

PEX1 p.Cys103Arg (c.307T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PEX1 p.Cys103Arg (c.307T>C) in the general population?

PEX1 p.Cys103Arg (c.307T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PEX1 p.Cys103Arg (c.307T>C)?

AlphaMissense predicts likely pathogenic (score 0.9438) — an in-silico prediction, not a clinical call.

PEX1 p.Cys103Arg

c.307T>C · VCV3930921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9438 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9438	likely pathogenic · top 5% in PEX1
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -13.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	24.9	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 0.00134% African / African-American · 1/74,898 alleles

Overall 0.000657% 1/152,230 alleles · very rare

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.Cys103Arg
Coding: c.307T>C
MANE Select: NM_000466
Type: single nucleotide variant
Location: chr7:92519045 (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.Cys103= Likely benign ★ 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
PEX1 p.Gln582His Uncertain significance ★★ ⚠ same condition
PEX1 p.Gln732Arg 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-cys103arg (accessed [today's date]).

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