Is PIGM p.Phe94= (c.282T>C) pathogenic?

PIGM p.Phe94= (c.282T>C) is classified Uncertain significance in PIGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). Very rare (popmax 0.0011%, sas); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Phe94= (c.282T>C) in the general population?

PIGM p.Phe94= (c.282T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

PIGM p.Phe94=

Q: What condition is associated with PIGM p.Phe94= (c.282T>C)?

PIGM p.Phe94= (c.282T>C) 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.282T>C · VCV4778335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -1.8	GERP -5.3
Overall
CADD	5.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 0.000124% 2/1,612,640 alleles · very rare exomes 2/1,460,340 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	8.48e-05%	1,178,705

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.Phe94=
Coding: c.282T>C
MANE Select: NM_145167
Type: single nucleotide variant
Location: chr1:160031458 (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.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
PIGM p.His44Tyr 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-phe94 (accessed [today's date]).

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