Is PYROXD2 p.Gln97Pro (c.290A>C) pathogenic?

PYROXD2 p.Gln97Pro (c.290A>C) is classified Uncertain significance in PYROXD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.2557); Ultra-rare (popmax 0.0387%, afr).

How common is PYROXD2 p.Gln97Pro (c.290A>C) in the general population?

PYROXD2 p.Gln97Pro (c.290A>C) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

What do computational predictors say about PYROXD2 p.Gln97Pro (c.290A>C)?

AlphaMissense predicts likely benign (score 0.2557) — an in-silico prediction, not a clinical call.

PYROXD2 p.Gln97Pro

c.290A>C · rs767134166 · VCV2371551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2557 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2557	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 31 kb · p 0.89 · regional, not allelic
Overall
CADD	23.1	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 0.0387% African / African-American · 29/74,970 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00204% 33/1,613,856 alleles · ultra-rare exomes 12/1,461,632 · genomes 21/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,585
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	8.47e-05%	1,179,974

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.Gln97Pro
Coding: c.290A>C
MANE Select: NM_032709
dbSNP: rs767134166
Type: single nucleotide variant
Location: chr10:98407607 (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-gln97pro (accessed [today's date]).

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