Is PIGM p.Pro348Ser (c.1042C>T) pathogenic?

PIGM p.Pro348Ser (c.1042C>T) is classified Benign in PIGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: ambiguous (0.4844); Low-frequency (popmax 1.76%, sas); Associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency.

What condition is associated with PIGM p.Pro348Ser (c.1042C>T)?

PIGM p.Pro348Ser (c.1042C>T) is associated with hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency (ClinVar).

How common is PIGM p.Pro348Ser (c.1042C>T) in the general population?

PIGM p.Pro348Ser (c.1042C>T) is low-frequency (popmax 1.76%, sas) (gnomAD).

What do computational predictors say about PIGM p.Pro348Ser (c.1042C>T)?

AlphaMissense predicts ambiguous (score 0.4844) — an in-silico prediction, not a clinical call.

PIGM p.Pro348Ser

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.1042C>T · rs201082832 · VCV2056194

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4844 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.76%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

Computational evidence

Protein change
AlphaMissense	0.4844	ambiguous
REVEL	0.267	benign-leaning
SaProt	LLR -8.06	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.4, 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

Grpmax group 1.76% South Asian · 1,601/91,074 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.66%

Overall 0.103% 1,666/1,614,062 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.76%	57
Remaining individualsnot grpmax-eligible	0.0864%	1,158
Middle Eastern	0.0495%	2,021
African / African-American	0.004%	25,018
European (non-Finnish)	0.000424%	235,981

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.Pro348Ser
Coding: c.1042C>T
MANE Select: NM_145167
dbSNP: rs201082832
Type: single nucleotide variant
Location: chr1:160030698 (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.Pro348Ala Uncertain significance ★★ ⚠ same residue
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

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-pro348ser (accessed [today's date]).

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