Is F7 p.Trp394Ter (c.1181G>A) pathogenic?

F7 p.Trp394Ter (c.1181G>A) is classified Likely pathogenic in F7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.000508%, nfe); Associated with F7-related disorder.

What condition is associated with F7 p.Trp394Ter (c.1181G>A)?

F7 p.Trp394Ter (c.1181G>A) is associated with F7-related disorder (ClinVar).

How common is F7 p.Trp394Ter (c.1181G>A) in the general population?

F7 p.Trp394Ter (c.1181G>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

F7 p.Trp394Ter

c.1181G>A · rs1460304955 · VCV3037080

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

F7-related disorder

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	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -0.43, phastCons 1
Overall
CADD	41.0	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 0.000508% European (non-Finnish) · 6/1,179,984 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,680 alleles · very rare

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.Trp394Ter
Coding: c.1181G>A
MANE Select: NM_019616
dbSNP: rs1460304955
Type: single nucleotide variant
Location: chr13:113118854 (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 394: a β-strand; the peptidase s1 domain

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

Disease context

F7-related disorder

Similar variants

F7 p.Ala332Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
F7 p.Thr397Met Pathogenic ★★ ⚠ same condition
F7 c.-32A>C Likely pathogenic ★ same condition
F7 p.Trp239Ter Likely pathogenic ★ same condition
F7 p.Asp280Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
F7 p.Cys173Tyr Uncertain significance ★ ⚠ same condition
F7 p.Val206Leu Uncertain significance ★ ⚠ same condition
F7 p.Arg342Gly 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-trp394ter (accessed [today's date]).

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