Is PAPSS2 p.Pro267= (c.801C>G) pathogenic?

PAPSS2 p.Pro267= (c.801C>G) is classified Likely benign in PAPSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Very rare (popmax 0.00267%, afr); Associated with spondyloepimetaphyseal dysplasia, PAPSS2 type.

What condition is associated with PAPSS2 p.Pro267= (c.801C>G)?

PAPSS2 p.Pro267= (c.801C>G) is associated with spondyloepimetaphyseal dysplasia, PAPSS2 type (ClinVar).

How common is PAPSS2 p.Pro267= (c.801C>G) in the general population?

PAPSS2 p.Pro267= (c.801C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Spondyloepimetaphyseal dysplasia, PAPSS2 type inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PAPSS2 p.Pro267=

c.801C>G · rs966311239 · VCV1128529

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

spondyloepimetaphyseal dysplasia, PAPSS2 type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -1.1, phastCons 0.018
Overall
CADD	9.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,898 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000744% 12/1,613,640 alleles · very rare exomes 11/1,461,484 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,449
European (non-Finnish)	0.000848%	117,971

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: PAPSS2
Protein: p.Pro267=
Coding: c.801C>G
MANE Select: NM_001015880
dbSNP: rs966311239
Type: single nucleotide variant
Location: chr10:87715779 (GRCh38)
Gene constraint: LOEUF 1.141 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.35 · 5 PDB
Residue 267: the 'sulfate adenylyltransferase' region; a turn

Full PAPSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondyloepimetaphyseal dysplasia, PAPSS2 type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spondyloepimetaphyseal dysplasia, PAPSS2 type (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PAPSS2 c.640-1G>C Pathogenic/Likely pathogenic ★★ same condition
PAPSS2 p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
PAPSS2 p.Arg334Ter Pathogenic ★★ same condition
PAPSS2 p.Arg41Ter Pathogenic ★★ same condition
PAPSS2 p.Tyr492Ter Pathogenic ★★ same condition
PAPSS2 p.Tyr74Ter Pathogenic/Likely pathogenic ★★ same condition
PAPSS2 p.Ala22Val Uncertain significance ★★ ⚠ same condition
PAPSS2 p.Ala409Thr 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/papss2-p-pro267 (accessed [today's date]).

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