Is PIGM p.Ser333= (c.999C>T) pathogenic?

PIGM p.Ser333= (c.999C>T) is classified Benign/Likely benign in PIGM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-23). Rare (popmax 0.521%, amr); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Ser333= (c.999C>T) in the general population?

PIGM p.Ser333= (c.999C>T) is rare (popmax 0.521%, amr) (gnomAD).

PIGM p.Ser333=

Q: What condition is associated with PIGM p.Ser333= (c.999C>T)?

PIGM p.Ser333= (c.999C>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.999C>T · rs187311473 · VCV1170560

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.521%, 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 0.35	GERP -3.7, phastCons 0.97
Overall
CADD	8.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.521% Admixed American · 313/60,028 alleles

Filtering AF 0.474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0406% 656/1,614,228 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.521%	192
Middle Eastern	0.066%	1,516
South Asian	0.0604%	1,656
Remaining individualsnot grpmax-eligible	0.0416%	2,404
European (non-Finnish)	0.0215%	4,646
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00266%	37,525
East Asian	0.00223%	44,894

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.Ser333=
Coding: c.999C>T
MANE Select: NM_145167
dbSNP: rs187311473
Type: single nucleotide variant
Location: chr1:160030741 (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-ser333 (accessed [today's date]).

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