Is PYROXD2 p.Ala470Val (c.1409C>T) pathogenic?

PYROXD2 p.Ala470Val (c.1409C>T) is classified Likely benign in PYROXD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0741); Absent from gnomAD v4.1.

How common is PYROXD2 p.Ala470Val (c.1409C>T) in the general population?

PYROXD2 p.Ala470Val (c.1409C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PYROXD2 p.Ala470Val (c.1409C>T)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

PYROXD2 p.Ala470Val

c.1409C>T · VCV4148775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.09	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 -1.5	GERP -2.6
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	2.961	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.Ala470Val
Coding: c.1409C>T
MANE Select: NM_032709
Type: single nucleotide variant
Location: chr10:98388392 (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-ala470val (accessed [today's date]).

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