Is F11 p.Trp73Ter (c.219G>A) pathogenic?

F11 p.Trp73Ter (c.219G>A) is classified Pathogenic/Likely pathogenic in F11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00111%, nfe); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Trp73Ter (c.219G>A)?

F11 p.Trp73Ter (c.219G>A) is associated with Plasma factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Trp73Ter (c.219G>A) in the general population?

F11 p.Trp73Ter (c.219G>A) is very rare (popmax 0.00111%, nfe) (gnomAD).

F11 p.Trp73Ter

c.219G>A · rs762013077 · VCV370221

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, nfe)

Conditions

Plasma factor XI 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-escape possible for C-terminal truncations
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 1.5, phastCons 1
Overall
CADD	38.0	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 0.00111% European (non-Finnish) · 13/1,170,062 alleles

Filtering AF 0.00062% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000478%

Overall 0.000874% 14/1,602,632 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,048
European (non-Finnish)grpmax	0.00111%	90,005

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: F11
Protein: p.Trp73Ter
Coding: c.219G>A
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs762013077
Type: single nucleotide variant
Location: chr4:186273071 (GRCh38)
Structure: AlphaFold pLDDT 68.98
Residue 73: the krab domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Plasma factor XI deficiency

Also linked: congenital factor XI deficiency

Similar variants

F11 p.Trp73Arg Uncertain significance ★ ⚠ same residue
F11 c.1136-1G>C Likely pathogenic ★★ same condition
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.595+3A>G Pathogenic/Likely pathogenic ★★ same condition
F11 c.755+2T>C 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/f11-p-trp73ter (accessed [today's date]).

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