Is F2 p.Arg314Ser (c.940C>A) pathogenic?

F2 p.Arg314Ser (c.940C>A) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely pathogenic (0.898); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F2 p.Arg314Ser (c.940C>A)?

F2 p.Arg314Ser (c.940C>A) is associated with Inborn genetic diseases (ClinVar).

How common is F2 p.Arg314Ser (c.940C>A) in the general population?

F2 p.Arg314Ser (c.940C>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about F2 p.Arg314Ser (c.940C>A)?

AlphaMissense predicts likely pathogenic (score 0.898) — an in-silico prediction, not a clinical call.

F2 p.Arg314Ser

c.940C>A · rs121918477 · VCV2273425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.898	likely pathogenic
REVEL	0.661	pathogenic-leaning
SaProt	LLR -5.25	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	22.2	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 0.000254% European (non-Finnish) · 3/1,179,958 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,062 alleles · very rare exomes 3/1,461,760 · genomes 0/152,302 · joint denominator

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: F2
Protein: p.Arg314Ser
Coding: c.940C>A
MANE Select: NM_000506
dbSNP: rs121918477
Type: single nucleotide variant
Location: chr11:46726563 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 314: a functional site (cleavage; by factor xa); a UniProt-annotated variant site (in fa2d; barcelona/madrid); a UniProt-annotated variant site (in fa2d; padua-1)

Full F2 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

F2 p.Arg314His Likely pathogenic ★★ ⚠ same residue
F2 p.Arg314Cys Pathogenic ★ same residue
F2 p.Ala490Thr Uncertain significance ★★ ⚠ same condition
F2 p.Arg217Gln Uncertain significance ★★ ⚠ same condition
F2 p.Arg224Cys Uncertain significance ★★ ⚠ same condition
F2 p.Arg35Trp Uncertain significance ★★ ⚠ same condition
F2 p.Ile438Thr Uncertain significance ★★ ⚠ same condition
F2 p.Pro471Thr 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/f2-p-arg314ser (accessed [today's date]).

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