Is F8 p.Arg590Ser (c.1770G>T) pathogenic?

F8 p.Arg590Ser (c.1770G>T) is classified Pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.7071); Absent from gnomAD v4.1; Associated with inherited thrombophilia.

What condition is associated with F8 p.Arg590Ser (c.1770G>T)?

F8 p.Arg590Ser (c.1770G>T) is associated with inherited thrombophilia (ClinVar).

How common is F8 p.Arg590Ser (c.1770G>T) in the general population?

F8 p.Arg590Ser (c.1770G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Arg590Ser (c.1770G>T)?

AlphaMissense predicts likely pathogenic (score 0.7071) — an in-silico prediction, not a clinical call.

F8 p.Arg590Ser

c.1770G>T · VCV4282514

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7071 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited thrombophilia

Computational evidence

Protein change
AlphaMissense	0.7071	likely pathogenic ✓ concordant with ClinVar
REVEL	0.614	indeterminate
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.83	GERP -0.83, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	22.2	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: F8
Protein: p.Arg590Ser
Coding: c.1770G>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154954025 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 590: the plastocyanin-like 4 domain; the f5/8 type a 2 domain

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited thrombophilia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F8 c.6429+2T>A Pathogenic ★★★ same type
F8 p.Ala111Thr Likely pathogenic ★★★ same type
F8 p.Ala2220Pro Pathogenic ★★★ same type
F8 p.Ala415Asp Likely pathogenic ★★★ same type
F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
F8 p.Arg1800His Pathogenic ★★★ same type
F8 p.Arg2016Trp 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/f8-p-arg590ser (accessed [today's date]).

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