Is F8 p.Arg301= (c.903C>T) pathogenic?

F8 p.Arg301= (c.903C>T) is classified Likely benign in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). Very rare (popmax 0.00302%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F8 p.Arg301= (c.903C>T)?

F8 p.Arg301= (c.903C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Arg301= (c.903C>T) in the general population?

F8 p.Arg301= (c.903C>T) is very rare (popmax 0.00302%, nfe) (gnomAD).

F8 p.Arg301=

c.903C>T · VCV4252405

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00302%, nfe)

Conditions

Inborn genetic diseases

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 0.7	GERP -2, phastCons 1
Overall
CADD	5.984	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00302% European (non-Finnish) · 27/895,135 alleles

Filtering AF 0.00206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00264% 29/1,097,804 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0042%	23,821
European (non-Finnish)grpmax	0.00302%	33,153

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg301=
Coding: c.903C>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154969437 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 301: a UniProt-annotated variant site (in hema; severe/mild); a UniProt-annotated variant site (in hema; severe); a disulfide bond; a β-strand; the f5/8 type a 1 domain; the plastocyanin-like 2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F8 p.Arg301His Pathogenic ★★ ⚠ same residue
F8 p.Arg301Cys Pathogenic ★ same residue
F8 p.Arg301Leu Pathogenic ★ ⚠ same residue
F8 p.Tyr1699Phe Pathogenic ★★ ⚠ same condition
F8 p.Ala2108Val Uncertain significance ★★ ⚠ same condition
F8 p.Gln1049Lys Uncertain significance ★★ ⚠ same condition
F8 p.Gln1209Arg Uncertain significance ★★ ⚠ same condition
F8 p.Gly1729Trp Uncertain significance ★★ ⚠ 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-arg301 (accessed [today's date]).

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