Is F5 p.Pro1045= (c.3135G>T) pathogenic?

F5 p.Pro1045= (c.3135G>T) is classified Likely benign in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). Ultra-rare (popmax 0.03%, amr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro1045= (c.3135G>T)?

F5 p.Pro1045= (c.3135G>T) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Pro1045= (c.3135G>T) in the general population?

F5 p.Pro1045= (c.3135G>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

F5 p.Pro1045=

c.3135G>T · rs760055896 · VCV1728005

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.7
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/59,988 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00112% 18/1,613,924 alleles · ultra-rare exomes 17/1,461,774 · genomes 1/152,150 · joint denominator

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: F5
Protein: p.Pro1045=
Coding: c.3135G>T
MANE Select: NM_000130
dbSNP: rs760055896
Type: single nucleotide variant
Location: chr1:169541955 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1045: the 'b' region; the 'disordered' region

Full F5 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

F5 p.Pro1045Leu Uncertain significance ★ ⚠ same residue
F5 p.Arg441His Uncertain significance ★★ ⚠ same condition
F5 p.Asn1559Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asn1575Ser Uncertain significance ★★ ⚠ same condition
F5 p.Asp1739Gly Uncertain significance ★★ ⚠ same condition
F5 p.Glu2029Asp Uncertain significance ★★ ⚠ same condition
F5 p.Glu48Gln Uncertain significance ★★ ⚠ same condition
F5 p.His812Tyr 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/f5-p-pro1045 (accessed [today's date]).

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