Is F2 p.Glu348Asp (c.1044G>C) pathogenic?

F2 p.Glu348Asp (c.1044G>C) is classified Uncertain significance in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1635); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F2 p.Glu348Asp (c.1044G>C)?

F2 p.Glu348Asp (c.1044G>C) is associated with Inborn genetic diseases (ClinVar).

How common is F2 p.Glu348Asp (c.1044G>C) in the general population?

F2 p.Glu348Asp (c.1044G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F2 p.Glu348Asp (c.1044G>C)?

AlphaMissense predicts likely benign (score 0.1635) — an in-silico prediction, not a clinical call.

F2 p.Glu348Asp

c.1044G>C · VCV4619031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1635 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1635	likely benign
REVEL	0.26	benign-leaning
SaProt	LLR -7.79	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 0.72	GERP 0.55, phastCons 0.067
Regional constraint	o/e 0.76	unconstrained · MANE · 20 kb · p 1.8e-12 · regional, not allelic
Overall
CADD	10.44	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: F2
Protein: p.Glu348Asp
Coding: c.1044G>C
MANE Select: NM_000506
Type: single nucleotide variant
Location: chr11:46726751 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 348: an α-helix; a disulfide bond

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.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
F2 p.Thr488Met Uncertain significance ★★ ⚠ same condition
F2 p.Val258Leu 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-glu348asp (accessed [today's date]).

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