Is PDXK p.Pro142= (c.426G>A) pathogenic?

PDXK p.Pro142= (c.426G>A) is classified Benign in PDXK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-25). Low-frequency (popmax 2.46%, mid); Associated with PDXK-related disorder.

What condition is associated with PDXK p.Pro142= (c.426G>A)?

PDXK p.Pro142= (c.426G>A) is associated with PDXK-related disorder (ClinVar).

How common is PDXK p.Pro142= (c.426G>A) in the general population?

PDXK p.Pro142= (c.426G>A) is low-frequency (popmax 2.46%, mid) (gnomAD).

PDXK p.Pro142=

c.426G>A · rs61737062 · VCV3055680

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.46%, mid)

Conditions

PDXK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.6
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.46% Middle Eastern · 149/6,058 alleles

Filtering AF 2.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.02%

Overall 1.57% 25,222/1,611,278 alleles · low-frequency exomes 23,073/1,458,920 · genomes 2,149/152,358 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.48%	40
Middle Easterngrpmax	2.46%	41
European (non-Finnish)	1.78%	56
Amishnot grpmax-eligible	1.76%	57
Remaining individualsnot grpmax-eligible	1.63%	61
Ashkenazi Jewishnot grpmax-eligible	1.33%	75
Admixed American	1.1%	91
African / African-American	0.315%	318
South Asian	0.224%	446
East Asian	0.00892%	11,216

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PDXK
Protein: p.Pro142=
Coding: c.426G>A
MANE Select: NM_003681
dbSNP: rs61737062
Type: single nucleotide variant
Location: chr21:43749042 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 10 PDB
Residue 142: an α-helix

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

Disease context

PDXK-related disorder

Similar variants

PDXK p.Ala228Thr Pathogenic ★★ ⚠ same condition
PDXK c.143-100C>T Uncertain significance same condition
PDXK c.*8G>A Benign same condition
PDXK p.Ala211Thr Uncertain significance ★★ ⚠ same type
PDXK p.Ala37Val Uncertain significance ★★ ⚠ same type
PDXK p.Gly281Glu Uncertain significance ★★ ⚠ same type
PDXK p.Met126Thr Uncertain significance ★★ ⚠ same type
PDXK c.142+3058C>T Likely benign ★★ 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/pdxk-p-pro142 (accessed [today's date]).

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