Is PIGM p.Ser101Arg (c.303C>A) pathogenic?

PIGM p.Ser101Arg (c.303C>A) is classified Uncertain significance in PIGM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely pathogenic (0.9116); Absent from gnomAD v4.1; Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

How common is PIGM p.Ser101Arg (c.303C>A) in the general population?

PIGM p.Ser101Arg (c.303C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIGM p.Ser101Arg (c.303C>A)?

AlphaMissense predicts likely pathogenic (score 0.9116) — an in-silico prediction, not a clinical call.

PIGM p.Ser101Arg

Q: What condition is associated with PIGM p.Ser101Arg (c.303C>A)?

PIGM p.Ser101Arg (c.303C>A) 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.303C>A · rs1193547806 · VCV2878457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

Computational evidence

Protein change
AlphaMissense	0.9116	likely pathogenic
REVEL	0.167	moderately benign-leaning
SaProt	LLR -11.87	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,268 bp · p 0.65 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PIGM
Protein: p.Ser101Arg
Coding: c.303C>A
MANE Select: NM_145167
dbSNP: rs1193547806
Type: single nucleotide variant
Location: chr1:160031437 (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-ser101arg (accessed [today's date]).

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