Is PYROXD2 p.Gln147Pro (c.440A>C) pathogenic?

PYROXD2 p.Gln147Pro (c.440A>C) is classified Uncertain significance in PYROXD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely pathogenic (0.8678); Absent from gnomAD v4.1.

How common is PYROXD2 p.Gln147Pro (c.440A>C) in the general population?

PYROXD2 p.Gln147Pro (c.440A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYROXD2 p.Gln147Pro (c.440A>C)?

AlphaMissense predicts likely pathogenic (score 0.8678) — an in-silico prediction, not a clinical call.

PYROXD2 p.Gln147Pro

c.440A>C · rs2496479024 · VCV2241869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8678 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8678	likely pathogenic
REVEL	0.21	benign-leaning
SaProt	LLR -13.87	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.1	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

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: PYROXD2
Protein: p.Gln147Pro
Coding: c.440A>C
MANE Select: NM_032709
dbSNP: rs2496479024
Type: single nucleotide variant
Location: chr10:98400133 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.56

Full PYROXD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PYROXD2 c.1062+2T>G Uncertain significance ★ same type
PYROXD2 p.Ala172Asp Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala293Val Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala303Ser Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala312Val Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala389Val Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala390Val Uncertain significance ★ ⚠ same type
PYROXD2 p.Ala524Thr Uncertain significance ★ ⚠ 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/pyroxd2-p-gln147pro (accessed [today's date]).

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