Is PYROXD2 p.Ala245Val (c.734C>T) pathogenic?

PYROXD2 p.Ala245Val (c.734C>T) is classified Uncertain significance in PYROXD2 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.4601); Very rare (popmax 0.00223%, eas); Associated with Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 related mitochanodrial defect.

How common is PYROXD2 p.Ala245Val (c.734C>T) in the general population?

PYROXD2 p.Ala245Val (c.734C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PYROXD2 p.Ala245Val (c.734C>T)?

AlphaMissense predicts ambiguous (score 0.4601) — an in-silico prediction, not a clinical call.

PYROXD2 p.Ala245Val

Q: What condition is associated with PYROXD2 p.Ala245Val (c.734C>T)?

PYROXD2 p.Ala245Val (c.734C>T) is associated with Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 related mitochanodrial defect (ClinVar).

c.734C>T · VCV3897907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 related mitochanodrial defect

⚠ 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	0.4601	ambiguous
REVEL	0.596	indeterminate
SaProt	LLR -8.82	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	26.3	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 0.00223% East Asian · 1/44,882 alleles

Overall 0.000186% 3/1,614,176 alleles · very rare exomes 3/1,461,894 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Remaining individualsnot grpmax-eligible	0.0016%	62,512
South Asian	0.0011%	91,080

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.Ala245Val
Coding: c.734C>T
MANE Select: NM_032709
Type: single nucleotide variant
Location: chr10:98395247 (GRCh38)

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

Disease context

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 related mitochanodrial defect

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-ala245val (accessed [today's date]).

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