Is F5 p.Pro794Ser (c.2380C>T) pathogenic?

F5 p.Pro794Ser (c.2380C>T) is classified Uncertain significance in F5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-09). AlphaMissense: likely benign (0.0893); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Pro794Ser (c.2380C>T)?

F5 p.Pro794Ser (c.2380C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F5 p.Pro794Ser (c.2380C>T) in the general population?

F5 p.Pro794Ser (c.2380C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about F5 p.Pro794Ser (c.2380C>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

F5 p.Pro794Ser

c.2380C>T · rs780727212 · VCV3047631

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -5.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	0.827	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 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,614,082 alleles · very rare exomes 17/1,461,834 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
African / African-American	0.00133%	75,012
European (non-Finnish)	0.00119%	84,286

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.Pro794Ser
Coding: c.2380C>T
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

Similar variants

F5 p.Pro794Thr 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-pro794ser (accessed [today's date]).

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