Is F8 p.Arg1985fs (c.5954del) pathogenic?

F8 p.Arg1985fs (c.5954del) is classified Pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-11). Absent from gnomAD.

How common is F8 p.Arg1985fs (c.5954del) in the general population?

F8 p.Arg1985fs (c.5954del) is absent from gnomAD (gnomAD).

F8 p.Arg1985fs

c.5954del · rs1215569190 · VCV618105

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 18 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.55	GERP -1.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: F8
Protein: p.Arg1985fs
Coding: c.5954del
MANE Select: NM_000132
dbSNP: rs1215569190
Type: Deletion
Location: chrX:154903950 (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

Similar variants

F8 p.Arg1985Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
F8 p.Arg1985Ter Pathogenic ★★ same residue
F8 p.Arg1985Gly Likely pathogenic ★ same residue
F8 p.Arg1985Pro Likely pathogenic ★ ⚠ same residue
F8 p.Ile1213fs Pathogenic ★★★ same type
F8 p.Ile1374fs Pathogenic ★★★ same type
F8 p.Ile567fs Pathogenic ★★★ same type
F8 c.2113+461_2113+473del 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-arg1985fs (accessed [today's date]).

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