Is F5 p.Met2016Ile (c.6048G>A) pathogenic?

F5 p.Met2016Ile (c.6048G>A) is classified Pathogenic in F5 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.5337); Absent from gnomAD v4.1; Associated with congenital factor V deficiency.

What condition is associated with F5 p.Met2016Ile (c.6048G>A)?

F5 p.Met2016Ile (c.6048G>A) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Met2016Ile (c.6048G>A) in the general population?

F5 p.Met2016Ile (c.6048G>A) is absent from gnomAD v4.1 (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.Met2016Ile (c.6048G>A)?

AlphaMissense predicts ambiguous (score 0.5337) — an in-silico prediction, not a clinical call.

F5 p.Met2016Ile

c.6048G>A · VCV3393327

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5337 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.5337	ambiguous
REVEL	0.509	indeterminate
SaProt	LLR -6.15	tolerated
Splicing
SpliceAI	Δ0.38	donor loss · deltas
Pangolin	Δ0.79	loss · gain 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 26 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	33.0	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

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.Met2016Ile
Coding: c.6048G>A
MANE Select: NM_000130
Type: single nucleotide variant
Location: chr1:169523197 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 2016: the f5/8 type c 1 domain

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)

Similar variants

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F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Asp96His Pathogenic ★★ 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-met2016ile (accessed [today's date]).

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