Is PROS1 p.Arg111fs (c.329dup) pathogenic?

PROS1 p.Arg111fs (c.329dup) is classified Likely pathogenic in PROS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). No gnomAD frequency available for this variant.

How common is PROS1 p.Arg111fs (c.329dup) in the general population?

PROS1 p.Arg111fs (c.329dup) is no gnomAD frequency available for this variant (gnomAD).

PROS1 p.Arg111fs

c.329dup · rs2472148844 · VCV2683289

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -3.5
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PROS1
Protein: p.Arg111fs
Coding: c.329dup
MANE Select: NM_000313
dbSNP: rs2472148844
Type: Duplication
Location: chr3:93910635 (GRCh38)
Gene constraint: LOEUF 0.53 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 83.06 · 3 PDB
Residue 111: the 'thrombin-sensitive' region; a UniProt-annotated variant site (in thph5)

Full PROS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PROS1 p.Leu17fs Likely pathogenic ★★ same type
PROS1 p.Asn418fs Pathogenic ★ same type
PROS1 p.Cys265fs Pathogenic ★ same type
PROS1 p.Cys88fs Likely pathogenic ★ same type
PROS1 p.His346fs Likely pathogenic ★ same type
PROS1 p.His658_Asn659insHis Likely pathogenic ★ same type
PROS1 p.His664fs Pathogenic ★ same type
PROS1 p.Ile397Ter Pathogenic ★ same type

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/pros1-p-arg111fs (accessed [today's date]).

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