Is F7 p.Trp239Ter (c.716G>A) pathogenic?

F7 p.Trp239Ter (c.716G>A) is classified Likely pathogenic in F7 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-04). Very rare (popmax 0.00167%, amr); Associated with F7-related disorders.

What condition is associated with F7 p.Trp239Ter (c.716G>A)?

F7 p.Trp239Ter (c.716G>A) is associated with F7-related disorders (ClinVar).

How common is F7 p.Trp239Ter (c.716G>A) in the general population?

F7 p.Trp239Ter (c.716G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

F7 p.Trp239Ter

c.716G>A · VCV4920650

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

F7-related disorders

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 within the last 50 nt of the penultimate exon (7 of 8, 23 nt from its 3' end) — 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 0.99	GERP -2.8, phastCons 0.31
Overall
CADD	34.0	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 0.00167% Admixed American · 1/60,024 alleles

Overall 0.000657% 1/152,322 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.Trp239Ter
Coding: c.716G>A
MANE Select: NM_019616
Type: single nucleotide variant
Location: chr13:113117573 (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 239: a β-strand; a disulfide bond; the peptidase s1 domain

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

Disease context

F7-related disorders

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.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
F7 p.Gly194Cys 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-trp239ter (accessed [today's date]).

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