Is F5 p.Ser955fs (c.2862del) pathogenic?

F5 p.Ser955fs (c.2862del) is classified Pathogenic/Likely pathogenic in F5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-05-15). Ultra-rare (popmax 0.0285%, sas); Associated with factor V deficiency.

What condition is associated with F5 p.Ser955fs (c.2862del)?

F5 p.Ser955fs (c.2862del) is associated with factor V deficiency, congenital factor V deficiency (ClinVar).

How common is F5 p.Ser955fs (c.2862del) in the general population?

F5 p.Ser955fs (c.2862del) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

F5 p.Ser955fs

c.2862del · rs765982916 · VCV627051

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

factor V deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 1.9, phastCons 0.012
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0285% South Asian · 26/91,082 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00242% 39/1,614,108 alleles · ultra-rare exomes 38/1,461,818 · genomes 1/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)	0.000932%	107,272

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.Ser955fs
Coding: c.2862del
MANE Select: NM_000130
dbSNP: rs765982916
Type: Deletion
Location: chr1:169542228 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 955: the 'b' region

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

Disease context

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

Also linked: congenital factor V deficiency

Similar variants

F5 p.Ser955Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
F5 c.4962_4971+3del Likely pathogenic ★★ same condition
F5 p.Ile847fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Leu1267fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Leu1818fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Lys674fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Thr397_Tyr399del Uncertain significance ★★ same condition
F5 c.251-6del Benign/Likely benign ★★ 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-ser955fs (accessed [today's date]).

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