Is F8 p.Asp366Gly (c.1097A>G) pathogenic?

F8 p.Asp366Gly (c.1097A>G) is classified Uncertain significance in F8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-01). AlphaMissense: likely benign (0.117); Absent from gnomAD v4.1; Associated with hemophilia A.

What condition is associated with F8 p.Asp366Gly (c.1097A>G)?

F8 p.Asp366Gly (c.1097A>G) is associated with hemophilia A (ClinVar).

How common is F8 p.Asp366Gly (c.1097A>G) in the general population?

F8 p.Asp366Gly (c.1097A>G) 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.

What do computational predictors say about F8 p.Asp366Gly (c.1097A>G)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

F8 p.Asp366Gly

c.1097A>G · VCV3573004

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hemophilia A

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.32, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	19.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asp366Gly
Coding: c.1097A>G
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154966600 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB

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 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
F8 p.Arg1768His Pathogenic ★★★ ⚠ same condition
F8 p.Arg1800His Pathogenic ★★★ same condition
F8 p.Arg2016Trp 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-asp366gly (accessed [today's date]).

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