Is SERPINC1 p.Pro384= (c.1152A>G) pathogenic?

SERPINC1 p.Pro384= (c.1152A>G) is classified Uncertain significance in SERPINC1 (ClinVar, Expert panel, 1 submitter; last evaluated 2024-01-25). Very rare (popmax 6.84e-05%); Associated with hereditary antithrombin deficiency.

What condition is associated with SERPINC1 p.Pro384= (c.1152A>G)?

SERPINC1 p.Pro384= (c.1152A>G) is associated with hereditary antithrombin deficiency (ClinVar).

How common is SERPINC1 p.Pro384= (c.1152A>G) in the general population?

SERPINC1 p.Pro384= (c.1152A>G) is very rare (popmax 6.84e-05%) (gnomAD).

SERPINC1 p.Pro384=

Q: How is Hereditary thrombophilia due to congenital antithrombin deficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1152A>G · rs2526569034 · VCV3242378

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

hereditary antithrombin deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.76	donor gain · deltas
Pangolin	Δ0.58	loss · gain 0.41 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP -1.1	GERP -0.076, phastCons 0.003
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,400 alleles · very rare

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: SERPINC1
Protein: p.Pro384=
Coding: c.1152A>G
MANE Select: NM_000488
dbSNP: rs2526569034
Type: single nucleotide variant
Location: chr1:173909553 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.34 · 27 PDB
Residue 384: a disulfide bond; a turn; a UniProt-annotated variant site (in at3d)

Full SERPINC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary antithrombin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary thrombophilia due to congenital antithrombin deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

SERPINC1 c.1154-14G>A Pathogenic ★★★ same condition
SERPINC1 c.1218+2T>C Likely pathogenic ★★★ same condition
SERPINC1 c.1219-2A>G Likely pathogenic ★★★ same condition
SERPINC1 c.624+1G>A Likely pathogenic ★★★ same condition
SERPINC1 p.Ala414Thr Likely pathogenic ★★★ same condition
SERPINC1 p.Ala416Pro Pathogenic ★★★ same condition
SERPINC1 p.Ala416Ser Pathogenic ★★★ ⚠ same condition
SERPINC1 p.Ala436Thr Likely pathogenic ★★★ ⚠ 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/serpinc1-p-pro384 (accessed [today's date]).

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