Is F8 p.Ser2192Arg (c.6576T>A) pathogenic?

F8 p.Ser2192Arg (c.6576T>A) is classified Likely pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-14). AlphaMissense: likely pathogenic (0.6437); Absent from gnomAD v4.1; Associated with F8-related disorder.

What condition is associated with F8 p.Ser2192Arg (c.6576T>A)?

F8 p.Ser2192Arg (c.6576T>A) is associated with F8-related disorder (ClinVar).

How common is F8 p.Ser2192Arg (c.6576T>A) in the general population?

F8 p.Ser2192Arg (c.6576T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Ser2192Arg (c.6576T>A)?

AlphaMissense predicts likely pathogenic (score 0.6437) — an in-silico prediction, not a clinical call.

F8 p.Ser2192Arg

c.6576T>A · rs2523839448 · VCV2635321

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

F8-related disorder

Computational evidence

Protein change
AlphaMissense	0.6437	likely pathogenic ✓ concordant with ClinVar
REVEL	0.749	pathogenic-leaning
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	Δ0.20	acceptor gain, 6 bp away · masked 0 · deltas
Pangolin	Δ0.21	gain · loss 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.39, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 91 kb · p 1.5e-14 · regional, not allelic
Overall
CADD	23.5	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.Ser2192Arg
Coding: c.6576T>A
MANE Select: NM_000132
dbSNP: rs2523839448
Type: single nucleotide variant
Location: chrX:154861865 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 2192: a UniProt-annotated variant site (in hema; mild)

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

Disease context

F8-related disorder

Similar variants

F8 p.Arg1708Cys Pathogenic ★★ ⚠ same condition
F8 p.Arg1960Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 p.Arg2169His Pathogenic ★★ ⚠ same condition
F8 p.Arg2326Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 p.Arg602Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 p.Arg717Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
F8 p.Glu291Lys Pathogenic ★★ ⚠ same condition
F8 p.Tyr1802Cys Pathogenic/Likely 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/f8-p-ser2192arg (accessed [today's date]).

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