Is PXMP4 p.Arg19Pro (c.56G>C) pathogenic?

PXMP4 p.Arg19Pro (c.56G>C) is classified Uncertain significance in PXMP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: ambiguous (0.434); Ultra-rare (popmax 0.0658%, mid).

How common is PXMP4 p.Arg19Pro (c.56G>C) in the general population?

PXMP4 p.Arg19Pro (c.56G>C) is ultra-rare (popmax 0.0658%, mid) (gnomAD).

What do computational predictors say about PXMP4 p.Arg19Pro (c.56G>C)?

AlphaMissense predicts ambiguous (score 0.434) — an in-silico prediction, not a clinical call.

PXMP4 p.Arg19Pro

c.56G>C · rs1258235997 · VCV3150124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.434 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.434	ambiguous
REVEL	0.171	moderately benign-leaning
SaProt	LLR -12.90	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 12 kb · p 0.024 · regional, not allelic
Overall
CADD	24.1	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 0.0658% Middle Eastern · 4/6,080 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.000682% 11/1,613,424 alleles · ultra-rare exomes 10/1,461,156 · genomes 1/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0658%	1,520
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.000509%	196,653

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: PXMP4
Protein: p.Arg19Pro
Coding: c.56G>C
MANE Select: NM_007238
dbSNP: rs1258235997
Type: single nucleotide variant
Location: chr20:33720152 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.79

Full PXMP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PXMP4 p.Ala161Val Uncertain significance ★ same type
PXMP4 p.Ala16Ser Uncertain significance ★ ⚠ same type
PXMP4 p.Ala48Val Uncertain significance ★ ⚠ same type
PXMP4 p.Ala9Thr Uncertain significance ★ ⚠ same type
PXMP4 p.Arg209Cys Uncertain significance ★ ⚠ same type
PXMP4 p.Arg209Gly Uncertain significance ★ ⚠ same type
PXMP4 p.Arg56Gln Uncertain significance ★ ⚠ same type
PXMP4 p.Arg80Gln 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/pxmp4-p-arg19pro (accessed [today's date]).

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