Is PIGM p.Arg60= (c.180C>T) pathogenic?

PIGM p.Arg60= (c.180C>T) is classified Benign/Likely benign in PIGM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.64%, nfe); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Arg60= (c.180C>T) in the general population?

PIGM p.Arg60= (c.180C>T) is low-frequency (popmax 2.64%, nfe) (gnomAD).

PIGM p.Arg60=

Q: What condition is associated with PIGM p.Arg60= (c.180C>T)?

PIGM p.Arg60= (c.180C>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.180C>T · rs41265753 · VCV1167407

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.64%, nfe)

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 -0.96	GERP -5
Overall
CADD	4.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.64% European (non-Finnish) · 31,129/1,180,038 alleles

Filtering AF 2.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.6%

Overall 2.2% 35,483/1,614,196 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.62%	28
European (non-Finnish)grpmax	2.64%	38
Remaining individualsnot grpmax-eligible	1.9%	53
Finnishnot grpmax-eligible	1.33%	75
Admixed American	1.13%	89
South Asian	1.12%	90
Ashkenazi Jewishnot grpmax-eligible	0.844%	118
Middle Eastern	0.479%	209
African / African-American	0.409%	244
East Asian	0.00891%	11,220

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg60=
Coding: c.180C>T
MANE Select: NM_145167
dbSNP: rs41265753
Type: single nucleotide variant
Location: chr1:160031560 (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-arg60 (accessed [today's date]).

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