Is F12 p.Arg593= (c.1779C>T) pathogenic?

F12 p.Arg593= (c.1779C>T) is classified Likely benign in F12 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-13). Absent from gnomAD v4.1.

How common is F12 p.Arg593= (c.1779C>T) in the general population?

F12 p.Arg593= (c.1779C>T) is absent from gnomAD v4.1 (gnomAD).

F12 p.Arg593=

c.1779C>T · rs1280601896 · VCV2814001

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.7	GERP -4.6, phastCons 0.98
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

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: F12
Protein: p.Arg593=
Coding: c.1779C>T
MANE Select: NM_000505
dbSNP: rs1280601896
Type: single nucleotide variant
Location: chr5:177402361 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 17 PDB
Residue 593: the peptidase s1 domain

Full F12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F12 p.Glu193Ter Pathogenic/Likely pathogenic ★★ same type
F12 p.Thr328Lys Pathogenic ★★ ⚠ same type
F12 c.57+4A>G Uncertain significance ★★ same type
F12 p.Ala452Thr Uncertain significance ★★ ⚠ same type
F12 p.Arg55Trp Uncertain significance ★★ ⚠ same type
F12 p.Asp283= Uncertain significance ★★ same type
F12 p.Glu288Lys Uncertain significance ★★ ⚠ same type
F12 p.Gly360Val Uncertain significance ★★ ⚠ 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/f12-p-arg593 (accessed [today's date]).

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