Is F8 p.Phe698Val (c.2092T>G) pathogenic?

F8 p.Phe698Val (c.2092T>G) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: ambiguous (0.5337); Absent from gnomAD v4.1.

How common is F8 p.Phe698Val (c.2092T>G) in the general population?

F8 p.Phe698Val (c.2092T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Phe698Val (c.2092T>G)?

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

F8 p.Phe698Val

c.2092T>G · rs2523932864 · VCV2920968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5337 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5337	ambiguous
REVEL	0.754	pathogenic-leaning
SaProt	LLR -5.57	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP -1.5, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic
Overall
CADD	24.2	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

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: F8
Protein: p.Phe698Val
Coding: c.2092T>G
MANE Select: NM_000132
dbSNP: rs2523932864
Type: single nucleotide variant
Location: chrX:154947719 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 698: the plastocyanin-like 4 domain; a UniProt-annotated variant site (in hema); a disulfide bond; a β-strand; the f5/8 type a 2 domain

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

F8 c.6429+2T>A Pathogenic ★★★ same type
F8 p.Ala111Thr Likely pathogenic ★★★ same type
F8 p.Ala2220Pro Pathogenic ★★★ same type
F8 p.Ala415Asp Likely pathogenic ★★★ same type
F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
F8 p.Arg1800His Pathogenic ★★★ same type
F8 p.Arg2016Trp Pathogenic ★★★ same type

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/f8-p-phe698val (accessed [today's date]).

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