Is F2 p.Asp595Glu (c.1785C>G) pathogenic?

F2 p.Asp595Glu (c.1785C>G) is classified Pathogenic in F2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-03-01). AlphaMissense: likely pathogenic (0.8671); Absent from gnomAD v4.1; Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Asp595Glu (c.1785C>G)?

F2 p.Asp595Glu (c.1785C>G) is associated with congenital prothrombin deficiency (ClinVar).

How common is F2 p.Asp595Glu (c.1785C>G) in the general population?

F2 p.Asp595Glu (c.1785C>G) is absent from gnomAD v4.1 (gnomAD).

How is Congenital factor II deficiency inherited?

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

What do computational predictors say about F2 p.Asp595Glu (c.1785C>G)?

AlphaMissense predicts likely pathogenic (score 0.8671) — an in-silico prediction, not a clinical call.

F2 p.Asp595Glu

c.1785C>G · rs121918486 · VCV13314

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital prothrombin deficiency

Computational evidence

Protein change
AlphaMissense	0.8671	likely pathogenic ✓ concordant with ClinVar
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -2.72	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.98, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	23.7	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: F2
Protein: p.Asp595Glu
Coding: c.1785C>G
MANE Select: NM_000506
dbSNP: rs121918486
Type: single nucleotide variant
Location: chr11:46739324 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 595: the peptidase s1 domain; a β-strand

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Congenital factor II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

F2 p.Asp595Asn Uncertain significance ★ ⚠ same residue
F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg596Gln Pathogenic ★★ ⚠ same condition
F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same condition
F2 c.559+5G>A Uncertain significance ★★ same condition
F2 p.Ala17Ser 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/f2-p-asp595glu (accessed [today's date]).

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