Is F8 p.Arg1985Ter (c.5953C>T) pathogenic?

F8 p.Arg1985Ter (c.5953C>T) is classified Pathogenic in F8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-01). Absent from gnomAD v4.1; Associated with hemophilia A.

What condition is associated with F8 p.Arg1985Ter (c.5953C>T)?

F8 p.Arg1985Ter (c.5953C>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Arg1985Ter (c.5953C>T) in the general population?

F8 p.Arg1985Ter (c.5953C>T) is absent from gnomAD v4.1 (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Arg1985Ter

c.5953C>T · rs137852452 · VCV10300

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hemophilia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 18 of 26
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.23, phastCons 0.9
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Arg1985Ter
Coding: c.5953C>T
MANE Select: NM_000132
dbSNP: rs137852452
Type: single nucleotide variant
Location: chrX:154903951 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1985: the f5/8 type a 3 domain; the plastocyanin-like 6 domain; a UniProt-annotated variant site (in hema; mild); a β-strand

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

Disease context

hemophilia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemophilia A (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

F8 p.Arg1985Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
F8 p.Arg1985Gly Likely pathogenic ★ same residue
F8 p.Arg1985Pro Likely pathogenic ★ ⚠ same residue
F8 c.6429+2T>A Pathogenic ★★★ same condition
F8 p.Ala111Thr Likely pathogenic ★★★ same condition
F8 p.Ala2220Pro Pathogenic ★★★ same condition
F8 p.Ala415Asp Likely pathogenic ★★★ same condition
F8 p.Ala415Val 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-arg1985ter (accessed [today's date]).

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