Is PIGV p.Pro293= (c.879G>A) pathogenic?

PIGV p.Pro293= (c.879G>A) is classified Conflicting classifications of pathogenicity in PIGV (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0826%, afr); Associated with hyperphosphatasia with intellectual disability syndrome 1.

What condition is associated with PIGV p.Pro293= (c.879G>A)?

PIGV p.Pro293= (c.879G>A) is associated with hyperphosphatasia with intellectual disability syndrome 1 (ClinVar).

How common is PIGV p.Pro293= (c.879G>A) in the general population?

PIGV p.Pro293= (c.879G>A) is ultra-rare (popmax 0.0826%, afr) (gnomAD).

PIGV p.Pro293=

Q: How is Hyperphosphatasia-intellectual disability syndrome inherited?

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

c.879G>A · rs147229452 · VCV384153

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, afr)

Conditions

hyperphosphatasia with intellectual disability syndrome 1

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 -9.3	GERP -4.5
Overall
CADD	0.141	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0826% African / African-American · 62/75,022 alleles

Filtering AF 0.0661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0602%

Overall 0.00601% 97/1,614,120 alleles · ultra-rare exomes 53/1,461,846 · genomes 44/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0826%	1,210
Admixed American	0.0183%	5,457
Remaining individualsnot grpmax-eligible	0.0128%	7,814
East Asian	0.00223%	44,882
South Asian	0.0022%	45,542
European (non-Finnish)	0.0011%	90,769

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: PIGV
Protein: p.Pro293=
Coding: c.879G>A
MANE Select: NM_017837
dbSNP: rs147229452
Type: single nucleotide variant
Location: chr1:26794913 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.22

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

Disease context

hyperphosphatasia with intellectual disability syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperphosphatasia-intellectual disability syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PIGV p.Ala341Glu Pathogenic/Likely pathogenic ★★ same condition
PIGV p.Arg19Cys Likely pathogenic ★★ ⚠ same condition
PIGV p.Arg203Cys Pathogenic/Likely pathogenic ★★ same condition
PIGV p.Cys156Tyr Pathogenic/Likely pathogenic ★★ same condition
PIGV p.Ala75Thr Uncertain significance ★★ ⚠ same condition
PIGV p.Arg270Cys Uncertain significance ★★ ⚠ same condition
PIGV p.Arg45His Uncertain significance ★★ ⚠ same condition
PIGV p.Asn327Ser 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/pigv-p-pro293 (accessed [today's date]).

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