Is F11 p.Trp73Arg (c.217T>C) pathogenic?

F11 p.Trp73Arg (c.217T>C) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.2653); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with F11 p.Trp73Arg (c.217T>C)?

F11 p.Trp73Arg (c.217T>C) is associated with Inborn genetic diseases (ClinVar).

How common is F11 p.Trp73Arg (c.217T>C) in the general population?

F11 p.Trp73Arg (c.217T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about F11 p.Trp73Arg (c.217T>C)?

AlphaMissense predicts likely benign (score 0.2653) — an in-silico prediction, not a clinical call.

F11 p.Trp73Arg

c.217T>C · VCV3511212

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2653	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -0.087, phastCons 0.98
Overall
CADD	15.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00031% 5/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,466
South Asian	0.0011%	91,094
European (non-Finnish)	0.000169%	590,009

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.Trp73Arg
Coding: c.217T>C
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186271770 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 73: a disulfide bond; the apple 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F11 p.Trp73Ter Pathogenic/Likely pathogenic ★★ same residue
F11 p.Asp69Gly Uncertain significance ★★ ⚠ same condition
F11 p.Ile537Leu Uncertain significance ★★ ⚠ same condition
F11 p.Thr407Ala Uncertain significance ★★ ⚠ same condition
F11 p.Val38Phe Uncertain significance ★★ ⚠ same condition
F11 p.Trp73fs Pathogenic ★ same residue
F11 p.Ala316Gly Uncertain significance ★ ⚠ same condition
F11 p.Ala337Thr Uncertain significance ★ ⚠ 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-trp73arg (accessed [today's date]).

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