Is F8 p.Ser1907Arg (c.5719A>C) pathogenic?

F8 p.Ser1907Arg (c.5719A>C) is classified Likely pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely pathogenic (0.9914); Absent from gnomAD v4.1; Associated with Factor VIII deficiency.

What condition is associated with F8 p.Ser1907Arg (c.5719A>C)?

F8 p.Ser1907Arg (c.5719A>C) is associated with Factor VIII deficiency (ClinVar).

How common is F8 p.Ser1907Arg (c.5719A>C) in the general population?

F8 p.Ser1907Arg (c.5719A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Ser1907Arg (c.5719A>C)?

AlphaMissense predicts likely pathogenic (score 0.9914) — an in-silico prediction, not a clinical call.

F8 p.Ser1907Arg

c.5719A>C · VCV4857322

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9914 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Factor VIII deficiency

Computational evidence

Protein change
AlphaMissense	0.9914	likely pathogenic ✓ concordant with ClinVar · top 1% in F8
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -16.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 91 kb · p 1.5e-14 · regional, not allelic
Overall
CADD	24.6	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.Ser1907Arg
Coding: c.5719A>C
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154904392 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1907: the f5/8 type a 3 domain; the plastocyanin-like 6 domain; a UniProt-annotated variant site (in hema; moderate); a UniProt-annotated variant site (in hema; severe)

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

Disease context

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

Similar variants

F8 p.Arg391His Pathogenic ★★ ⚠ same condition
F8 p.Arg546Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 p.Glu1701Lys Likely pathogenic ★★ ⚠ same condition
F8 p.His1973Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 c.144-5C>G Likely pathogenic ★ same condition
F8 c.601+5G>A Likely pathogenic ★ same condition
F8 p.Asn486Ser Likely pathogenic ★ same condition
F8 p.Gly190Asp 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/f8-p-ser1907arg (accessed [today's date]).

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