Is F8 p.Val1489= (c.4467C>G) pathogenic?

F8 p.Val1489= (c.4467C>G) is classified Benign/Likely benign in F8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-01). Rare (popmax 0.419%, afr); Associated with hemophilia A.

What condition is associated with F8 p.Val1489= (c.4467C>G)?

F8 p.Val1489= (c.4467C>G) is associated with hemophilia A (ClinVar).

How common is F8 p.Val1489= (c.4467C>G) in the general population?

F8 p.Val1489= (c.4467C>G) is rare (popmax 0.419%, afr) (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Val1489=

c.4467C>G · rs35207609 · VCV914834

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.419%, afr)

Conditions

hemophilia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.21, phastCons 0.042
Overall
CADD	0.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.419% African / African-American · 240/57,306 alleles

Filtering AF 0.375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.358%

Overall 0.022% 266/1,210,377 alleles · rare exomes 129/1,098,146 · genomes 137/112,231 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.419%	239
Admixed American	0.0306%	3,271
Remaining individualsnot grpmax-eligible	0.021%	4,761
South Asian	0.00176%	56,840
European (non-Finnish)	0.000112%	895,287

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: F8
Protein: p.Val1489=
Coding: c.4467C>G
MANE Select: NM_000132
dbSNP: rs35207609
Type: single nucleotide variant
Location: chrX:154929323 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1489: the 'b' region

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-val1489 (accessed [today's date]).

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