Is PIGM p.Leu98= (c.294C>T) pathogenic?

PIGM p.Leu98= (c.294C>T) is classified Likely benign in PIGM (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-23). Ultra-rare (popmax 0.01%, amr); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Leu98= (c.294C>T) in the general population?

PIGM p.Leu98= (c.294C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

PIGM p.Leu98=

Q: What condition is associated with PIGM p.Leu98= (c.294C>T)?

PIGM p.Leu98= (c.294C>T) 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.294C>T · rs750695305 · VCV734772

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, 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 0.21	GERP -5.3, phastCons 0.94
Overall
CADD	7.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,978 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,612,098 alleles · ultra-rare exomes 5/1,459,886 · genomes 1/152,212 · joint denominator

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.Leu98=
Coding: c.294C>T
MANE Select: NM_145167
dbSNP: rs750695305
Type: single nucleotide variant
Location: chr1:160031446 (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.Leu98Ile 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-leu98 (accessed [today's date]).

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