Is PXDN p.Pro552= (c.1656C>T) pathogenic?

PXDN p.Pro552= (c.1656C>T) is classified Benign/Likely benign in PXDN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-09). Ultra-rare (popmax 0.0818%, nfe); Associated with anterior segment dysgenesis 7.

What condition is associated with PXDN p.Pro552= (c.1656C>T)?

PXDN p.Pro552= (c.1656C>T) is associated with anterior segment dysgenesis 7 (ClinVar).

How common is PXDN p.Pro552= (c.1656C>T) in the general population?

PXDN p.Pro552= (c.1656C>T) is ultra-rare (popmax 0.0818%, nfe) (gnomAD).

PXDN p.Pro552=

c.1656C>T · rs200276592 · VCV772385

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0818%, nfe)

Conditions

anterior segment dysgenesis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.244	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4
Overall
CADD	0.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0818% European (non-Finnish) · 958/1,171,128 alleles

Filtering AF 0.0775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0757%

Overall 0.0719% 1,146/1,594,342 alleles · ultra-rare exomes 1,048/1,442,038 · genomes 98/152,304 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.156%	640
Remaining individualsnot grpmax-eligible	0.0874%	1,144
European (non-Finnish)grpmax	0.0818%	1,222
Admixed American	0.0263%	3,799
Middle Eastern	0.0167%	5,980
African / African-American	0.0147%	6,795
South Asian	0.0114%	8,753

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: PXDN
Protein: p.Pro552=
Coding: c.1656C>T
MANE Select: NM_012293
dbSNP: rs200276592
Type: single nucleotide variant
Location: chr2:1662096 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.43
Residue 552: the ig-like c2-type 4 domain

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

Disease context

anterior segment dysgenesis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PXDN p.Ala211Val Uncertain significance ★★ ⚠ same condition
PXDN p.Arg1376Cys Uncertain significance ★★ ⚠ same condition
PXDN p.Arg372Gln Uncertain significance ★★ ⚠ same condition
PXDN p.Arg597Trp Uncertain significance ★★ same condition
PXDN p.Arg84Gln Uncertain significance ★★ ⚠ same condition
PXDN p.Arg874Cys Uncertain significance ★★ ⚠ same condition
PXDN p.Asn655Ser Uncertain significance ★★ ⚠ same condition
PXDN p.Gln1362Pro Uncertain significance ★★ ⚠ same condition

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/pxdn-p-pro552 (accessed [today's date]).

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