Is PIGM p.Pro273= (c.819G>A) pathogenic?

PIGM p.Pro273= (c.819G>A) is classified Benign in PIGM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Low-frequency (popmax 2.23%, amr); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Pro273= (c.819G>A) in the general population?

PIGM p.Pro273= (c.819G>A) is low-frequency (popmax 2.23%, amr) (gnomAD).

PIGM p.Pro273=

Q: What condition is associated with PIGM p.Pro273= (c.819G>A)?

PIGM p.Pro273= (c.819G>A) is associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (ClinVar).

Q: How is Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency inherited?

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

c.819G>A · rs138151842 · VCV193498

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.23%, amr)

Conditions

hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

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 -20	GERP -4.8
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.23% Admixed American · 1,337/60,012 alleles

Filtering AF 2.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.09%

Overall 0.0872% 1,408/1,614,106 alleles · low-frequency exomes 1,205/1,461,878 · genomes 203/152,228 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.23%	45
Remaining individualsnot grpmax-eligible	0.088%	1,137
African / African-American	0.0147%	6,820
European (non-Finnish)	0.000424%	236,003

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: PIGM
Protein: p.Pro273=
Coding: c.819G>A
MANE Select: NM_145167
dbSNP: rs138151842
Type: single nucleotide variant
Location: chr1:160030921 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.10

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

Disease context

hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PIGM p.Pro273Leu Uncertain significance ★ same residue
PIGM p.Met1Thr Likely pathogenic ★★ same condition
PIGM p.Arg41Gln Uncertain significance ★★ ⚠ same condition
PIGM p.Arg46Lys Uncertain significance ★★ ⚠ same condition
PIGM p.Cys317Tyr Uncertain significance ★★ ⚠ same condition
PIGM p.Gln334Pro Uncertain significance ★★ ⚠ same condition
PIGM p.Glu217Gln Uncertain significance ★★ ⚠ same condition
PIGM p.Gly20Asp 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/pigm-p-pro273 (accessed [today's date]).

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