Is F5 p.Ser174= (c.522C>T) pathogenic?

F5 p.Ser174= (c.522C>T) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-30). Absent from gnomAD v4.1; Associated with factor V deficiency.

What condition is associated with F5 p.Ser174= (c.522C>T)?

F5 p.Ser174= (c.522C>T) is associated with factor V deficiency, thrombophilia due to thrombin defect, thrombophilia due to activated protein C resistance (ClinVar).

How common is F5 p.Ser174= (c.522C>T) in the general population?

F5 p.Ser174= (c.522C>T) is absent from gnomAD v4.1 (gnomAD).

F5 p.Ser174=

c.522C>T · rs777533725 · VCV875653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

factor V deficiency

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 1.8	GERP -1, phastCons 1
Overall
CADD	8.648	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F5
Protein: p.Ser174=
Coding: c.522C>T
MANE Select: NM_000130
dbSNP: rs777533725
Type: single nucleotide variant
Location: chr1:169560618 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 174: the f5/8 type a 1 domain; the plastocyanin-like 1 domain

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: thrombophilia due to thrombin defect thrombophilia due to activated protein C resistance Budd-Chiari syndrome

Similar variants

F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ same condition
F5 p.Ala38Thr Uncertain significance ★★ ⚠ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln 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-ser174 (accessed [today's date]).

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