Is F5 p.Pro794Thr (c.2380C>A) pathogenic?

F5 p.Pro794Thr (c.2380C>A) is classified Uncertain significance in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-19). AlphaMissense: likely benign (0.0726); Ultra-rare (popmax 0.0151%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro794Thr (c.2380C>A)?

F5 p.Pro794Thr (c.2380C>A) is associated with Inborn genetic diseases, congenital factor V deficiency (ClinVar).

How common is F5 p.Pro794Thr (c.2380C>A) in the general population?

F5 p.Pro794Thr (c.2380C>A) is ultra-rare (popmax 0.0151%, nfe) (gnomAD).

What do computational predictors say about F5 p.Pro794Thr (c.2380C>A)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

F5 p.Pro794Thr

c.2380C>A · rs780727212 · VCV2219109

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0151%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -0.85, phastCons 0.011
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	0.778	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0151% European (non-Finnish) · 178/1,180,004 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.0113% 182/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0151%	6,629
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00134%	74,890

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.Pro794Thr
Coding: c.2380C>A
MANE Select: NM_000130
dbSNP: rs780727212
Type: single nucleotide variant
Location: chr1:169542710 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 794: the 'b' 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

Also linked: congenital factor V deficiency

Similar variants

F5 p.Pro794Ser Uncertain significance ★ ⚠ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/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/f5-p-pro794thr (accessed [today's date]).

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