Is PYROXD1 p.Lys341Arg (c.1022A>G) pathogenic?

PYROXD1 p.Lys341Arg (c.1022A>G) is classified Uncertain significance in PYROXD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.075); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PYROXD1 p.Lys341Arg (c.1022A>G)?

PYROXD1 p.Lys341Arg (c.1022A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PYROXD1 p.Lys341Arg (c.1022A>G) in the general population?

PYROXD1 p.Lys341Arg (c.1022A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYROXD1 p.Lys341Arg (c.1022A>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

PYROXD1 p.Lys341Arg

c.1022A>G · VCV4148758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP -2.6, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 19 kb · p 2.6e-08 · regional, not allelic
Overall
CADD	16.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PYROXD1
Protein: p.Lys341Arg
Coding: c.1022A>G
MANE Select: NM_024854
Type: single nucleotide variant
Location: chr12:21462768 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 2 PDB
Residue 341: a β-strand

Full PYROXD1 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

PYROXD1 p.Ala393Val Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Asn52Asp Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Asp352Gly Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Asp466Asn Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Asp64Asn Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Asp64His Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Glu241Asp Uncertain significance ★★ ⚠ same condition
PYROXD1 p.Gly232Arg 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/pyroxd1-p-lys341arg (accessed [today's date]).

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