Is F7 p.Cys99Ter (c.297C>A) pathogenic?

F7 p.Cys99Ter (c.297C>A) is classified Pathogenic in F7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-10-01). Very rare (popmax 0.00223%, eas); Associated with factor VII deficiency.

What condition is associated with F7 p.Cys99Ter (c.297C>A)?

F7 p.Cys99Ter (c.297C>A) is associated with factor VII deficiency (ClinVar).

How common is F7 p.Cys99Ter (c.297C>A) in the general population?

F7 p.Cys99Ter (c.297C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

F7 p.Cys99Ter

c.297C>A · rs121964933 · VCV12084

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

factor VII deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -3.5
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,902 alleles

Overall 0.000124% 2/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,902
South Asian	0.0011%	91,092

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: F7
Protein: p.Cys99Ter
Coding: c.297C>A
MANE Select: NM_019616
dbSNP: rs121964933
Type: single nucleotide variant
Location: chr13:113113893 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 114 PDB
Residue 99: an α-helix; the gla domain

Full F7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor VII deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same condition
F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.-30A>C Likely pathogenic ★★ same condition
F7 c.-55C>T Pathogenic/Likely pathogenic ★★ same condition
F7 c.-61T>G Likely pathogenic ★★ same condition
F7 p.Ala282Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
F7 p.Ala332Val Pathogenic/Likely pathogenic ★★ same condition
F7 p.Ala407Thr Likely 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/f7-p-cys99ter (accessed [today's date]).

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