Is F5 p.Ser1149Phe (c.3446C>T) pathogenic?

F5 p.Ser1149Phe (c.3446C>T) is classified Likely benign in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). AlphaMissense: likely benign (0.1086); Rare (popmax 0.102%, eas); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Ser1149Phe (c.3446C>T)?

F5 p.Ser1149Phe (c.3446C>T) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Ser1149Phe (c.3446C>T) in the general population?

F5 p.Ser1149Phe (c.3446C>T) is rare (popmax 0.102%, eas) (gnomAD).

How is Congenital factor V deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F5 p.Ser1149Phe (c.3446C>T)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

F5 p.Ser1149Phe

c.3446C>T · rs559098136 · VCV1091728

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.01	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 0.91	GERP -1.5, phastCons 0.015
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	2.433	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 0.102% East Asian · 46/44,880 alleles

Filtering AF 0.0789% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0706%

Overall 0.00316% 51/1,614,152 alleles · rare exomes 42/1,461,826 · genomes 9/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.102%	976
Remaining individualsnot grpmax-eligible	0.0032%	31,254
South Asian	0.0011%	91,084
European (non-Finnish)	0.000169%	589,991

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.Ser1149Phe
Coding: c.3446C>T
MANE Select: NM_000130
dbSNP: rs559098136
Type: single nucleotide variant
Location: chr1:169541644 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1149: the 'b' region; the 'disordered' region

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor V deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor V deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

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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-ser1149phe (accessed [today's date]).

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