Is GPX1 p.Arg5Pro (c.14G>C) pathogenic?

GPX1 p.Arg5Pro (c.14G>C) is classified Benign in GPX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Low-frequency (popmax 3.24%, afr); Associated with GPX1-related disorder.

What condition is associated with GPX1 p.Arg5Pro (c.14G>C)?

GPX1 p.Arg5Pro (c.14G>C) is associated with GPX1-related disorder (ClinVar).

How common is GPX1 p.Arg5Pro (c.14G>C) in the general population?

GPX1 p.Arg5Pro (c.14G>C) is low-frequency (popmax 3.24%, afr) (gnomAD).

GPX1 p.Arg5Pro

c.14G>C · rs8179169 · VCV3056610

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.24%, afr)

Conditions

GPX1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.043	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3
Regional constraint	o/e 0.94	unconstrained · MANE · 887 bp · p 0.28 · regional, not allelic
Overall
CADD	5.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.24% African / African-American · 2,361/72,772 alleles

Filtering AF 3.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.09%

Overall 0.249% 3,831/1,541,366 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.24%	31
South Asian	0.751%	133
Middle Eastern	0.506%	198
Ashkenazi Jewishnot grpmax-eligible	0.398%	251
Remaining individualsnot grpmax-eligible	0.376%	266
Admixed American	0.289%	347
European (non-Finnish)	0.0297%	3,361
East Asian	0.00492%	20,321

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: GPX1
Protein: p.Arg5Pro
Coding: c.14G>C
MANE Select: NM_000581
dbSNP: rs8179169
Type: single nucleotide variant
Location: chr3:49358265 (GRCh38)
Gene constraint: LOEUF 1.38 · pLI <0.01 (gnomAD)
Residue 5: a UniProt-annotated variant site (in)

Full GPX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPX1-related disorder

Similar variants

GPX1 p.Arg5Trp Uncertain significance ★ same residue
GPX1 c.252+138G>C Uncertain significance same condition
GPX1 p.Ala194Thr Benign same condition
GPX1 p.Ala132Val Uncertain significance ★★ same type
GPX1 p.Ala140Ser Uncertain significance ★★ same type
GPX1 p.Ile42Thr Uncertain significance ★★ same type
GPX1 p.Pro190Ser Uncertain significance ★★ same type
GPX1 c.-46C>T Benign ★★ 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/gpx1-p-arg5pro (accessed [today's date]).

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