Is PXDN p.Val481= (c.1443C>A) pathogenic?

PXDN p.Val481= (c.1443C>A) is classified Likely benign in PXDN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-28). Rare (popmax 0.107%, afr); Associated with anterior segment dysgenesis 7.

What condition is associated with PXDN p.Val481= (c.1443C>A)?

PXDN p.Val481= (c.1443C>A) is associated with anterior segment dysgenesis 7 (ClinVar).

How common is PXDN p.Val481= (c.1443C>A) in the general population?

PXDN p.Val481= (c.1443C>A) is rare (popmax 0.107%, afr) (gnomAD).

PXDN p.Val481=

c.1443C>A · rs370752629 · VCV747125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.107%, afr)

Conditions

anterior segment dysgenesis 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.156	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.33	GERP -4, phastCons 0.034
Overall
CADD	4.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% African / African-American · 80/75,060 alleles

Filtering AF 0.0877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0808%

Overall 0.00676% 109/1,613,400 alleles · rare exomes 62/1,461,060 · genomes 47/152,340 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.107%	938
Remaining individualsnot grpmax-eligible	0.0208%	4,806
Admixed American	0.015%	6,670
South Asian	0.00329%	30,359
European (non-Finnish)	0.000339%	294,973

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.Val481=
Coding: c.1443C>A
MANE Select: NM_012293
dbSNP: rs370752629
Type: single nucleotide variant
Location: chr2:1663729 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.43
Residue 481: the ig-like c2-type 3 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-val481 (accessed [today's date]).

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