Is F2 p.Asp173Tyr (c.517G>T) pathogenic?

F2 p.Asp173Tyr (c.517G>T) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.3421); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F2 p.Asp173Tyr (c.517G>T)?

F2 p.Asp173Tyr (c.517G>T) is associated with Inborn genetic diseases (ClinVar).

How common is F2 p.Asp173Tyr (c.517G>T) in the general population?

F2 p.Asp173Tyr (c.517G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F2 p.Asp173Tyr (c.517G>T)?

AlphaMissense predicts ambiguous (score 0.3421) — an in-silico prediction, not a clinical call.

F2 p.Asp173Tyr

c.517G>T · VCV4020706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3421 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3421	ambiguous
REVEL	0.528	indeterminate
SaProt	LLR -8.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.89, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F2
Protein: p.Asp173Tyr
Coding: c.517G>T
MANE Select: NM_000506
Type: single nucleotide variant
Location: chr11:46723476 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 173: a disulfide bond; the kringle 1 domain; a β-strand

Full F2 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

F2 p.Asp173His Uncertain significance ★★ same residue
F2 p.Ala490Thr Uncertain significance ★★ ⚠ same condition
F2 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
F2 p.Arg224Cys Uncertain significance ★★ ⚠ same condition
F2 p.Arg35Trp Uncertain significance ★★ ⚠ same condition
F2 p.Ile438Thr Uncertain significance ★★ ⚠ same condition
F2 p.Pro471Thr Uncertain significance ★★ ⚠ same condition
F2 p.Thr488Met 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/f2-p-asp173tyr (accessed [today's date]).

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