Is F8 p.Asp34= (c.102C>T) pathogenic?

F8 p.Asp34= (c.102C>T) is classified Benign/Likely benign in F8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-10). Rare (popmax 0.18%, nfe); Associated with hemophilia A.

What condition is associated with F8 p.Asp34= (c.102C>T)?

F8 p.Asp34= (c.102C>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Asp34= (c.102C>T) in the general population?

F8 p.Asp34= (c.102C>T) is rare (popmax 0.18%, nfe) (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Asp34=

c.102C>T · rs1800283 · VCV618109

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.18%, nfe)

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 3.8	GERP 0.72, phastCons 1
Overall
CADD	5.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.18% European (non-Finnish) · 1,613/894,936 alleles

Filtering AF 0.173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.145% 1,757/1,208,720 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.18%	555
Ashkenazi Jewishnot grpmax-eligible	0.168%	595
Remaining individualsnot grpmax-eligible	0.151%	661
Finnishnot grpmax-eligible	0.0259%	3,858
African / African-American	0.0211%	4,732
Admixed American	0.0197%	5,072
South Asian	0.00353%	28,323

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.Asp34=
Coding: c.102C>T
MANE Select: NM_000132
dbSNP: rs1800283
Type: single nucleotide variant
Location: chrX:155022451 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 34: the f5/8 type a 1 domain; the plastocyanin-like 1 domain

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.Asp34Glu Uncertain significance ★ ⚠ same residue
F8 p.Asp34Asn Uncertain significance ★ ⚠ same residue
F8 p.Asp34Val Conflicting classifications of pathogenicity ★ ⚠ 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-asp34 (accessed [today's date]).

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