Is PIGM p.Gly2= (c.6C>T) pathogenic?

PIGM p.Gly2= (c.6C>T) is classified Benign/Likely benign in PIGM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-01). Low-frequency (popmax 2.66%, mid); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Gly2= (c.6C>T) in the general population?

PIGM p.Gly2= (c.6C>T) is low-frequency (popmax 2.66%, mid) (gnomAD).

PIGM p.Gly2=

Q: What condition is associated with PIGM p.Gly2= (c.6C>T)?

PIGM p.Gly2= (c.6C>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.6C>T · rs61757715 · VCV592292

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.66%, mid)

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 3.9	GERP 1.9, phastCons 0.76
Overall
CADD	10.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.66% Middle Eastern · 160/6,010 alleles

Filtering AF 2.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.2%

Overall 0.17% 2,743/1,614,124 alleles · low-frequency exomes 2,166/1,461,800 · genomes 577/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.66%	38
Amishnot grpmax-eligible	1.87%	54
Ashkenazi Jewishnot grpmax-eligible	1.49%	67
African / African-American	0.821%	122
Admixed American	0.565%	177
Remaining individualsnot grpmax-eligible	0.339%	295
European (non-Finnish)	0.0792%	1,262
South Asian	0.0231%	4,337
Finnishnot grpmax-eligible	0.00156%	64,032

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.Gly2=
Coding: c.6C>T
MANE Select: NM_145167
dbSNP: rs61757715
Type: single nucleotide variant
Location: chr1:160031734 (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-gly2 (accessed [today's date]).

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