Is F8 p.Ile1065Phe (c.3193A>T) pathogenic?

F8 p.Ile1065Phe (c.3193A>T) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1118); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with F8 p.Ile1065Phe (c.3193A>T)?

F8 p.Ile1065Phe (c.3193A>T) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Ile1065Phe (c.3193A>T) in the general population?

F8 p.Ile1065Phe (c.3193A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Ile1065Phe (c.3193A>T)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

F8 p.Ile1065Phe

c.3193A>T · VCV4252408

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -3.2, phastCons 0.011
Regional constraint	o/e 0.99	unconstrained · MANE · 2,842 bp · p 0.74 · regional, not allelic
Overall
CADD	3.247	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: F8
Protein: p.Ile1065Phe
Coding: c.3193A>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154930597 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1065: the 'b' region

Full F8 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

F8 p.Tyr1699Phe Pathogenic ★★ ⚠ same condition
F8 p.Ala2108Val Uncertain significance ★★ ⚠ same condition
F8 p.Gln1049Lys Uncertain significance ★★ ⚠ same condition
F8 p.Gln1209Arg Uncertain significance ★★ ⚠ same condition
F8 p.Gly1729Trp Uncertain significance ★★ ⚠ same condition
F8 p.Leu13Phe Uncertain significance ★★ ⚠ same condition
F8 p.Ser1968Asn Uncertain significance ★★ ⚠ same condition
F8 p.Thr1670Ile 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/f8-p-ile1065phe (accessed [today's date]).

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