Is PYROXD2 p.Val38Met (c.112G>A) pathogenic?

PYROXD2 p.Val38Met (c.112G>A) is classified Uncertain significance in PYROXD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: ambiguous (0.5205); Very rare (popmax 0.00898%, nfe).

How common is PYROXD2 p.Val38Met (c.112G>A) in the general population?

PYROXD2 p.Val38Met (c.112G>A) is very rare (popmax 0.00898%, nfe) (gnomAD).

What do computational predictors say about PYROXD2 p.Val38Met (c.112G>A)?

AlphaMissense predicts ambiguous (score 0.5205) — an in-silico prediction, not a clinical call.

PYROXD2 p.Val38Met

c.112G>A · rs151066099 · VCV2463407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5205	ambiguous
REVEL	0.382	indeterminate
SaProt	LLR -11.94	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.00898% European (non-Finnish) · 106/1,179,812 alleles

Filtering AF 0.00758% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00706%

Overall 0.00688% 111/1,613,632 alleles · very rare exomes 105/1,461,402 · genomes 6/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00898%	11,130
Remaining individualsnot grpmax-eligible	0.0064%	15,617
African / African-American	0.00133%	74,934

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: PYROXD2
Protein: p.Val38Met
Coding: c.112G>A
MANE Select: NM_032709
dbSNP: rs151066099
Type: single nucleotide variant
Location: chr10:98415024 (GRCh38)

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

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-val38met (accessed [today's date]).

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