Is F8 p.Pro947Ser (c.2839C>T) pathogenic?

F8 p.Pro947Ser (c.2839C>T) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.0728); Ultra-rare (popmax 0.0159%, afr); Associated with Inborn genetic diseases.

What condition is associated with F8 p.Pro947Ser (c.2839C>T)?

F8 p.Pro947Ser (c.2839C>T) is associated with Inborn genetic diseases (ClinVar).

How common is F8 p.Pro947Ser (c.2839C>T) in the general population?

F8 p.Pro947Ser (c.2839C>T) is ultra-rare (popmax 0.0159%, afr) (gnomAD).

What do computational predictors say about F8 p.Pro947Ser (c.2839C>T)?

AlphaMissense predicts likely benign (score 0.0728) — an in-silico prediction, not a clinical call.

F8 p.Pro947Ser

c.2839C>T · VCV3511321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0728	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -5.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.49	GERP -2.1, phastCons 0.035
Regional constraint	o/e 0.99	unconstrained · MANE · 2,842 bp · p 0.74 · regional, not allelic
Overall
CADD	0.368	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

Grpmax group 0.0159% African / African-American · 9/56,499 alleles

Filtering AF 0.00827% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0062%

Overall 0.000754% 9/1,194,081 alleles · ultra-rare exomes 2/1,082,319 · genomes 7/111,762 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: F8
Protein: p.Pro947Ser
Coding: c.2839C>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154930951 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 947: the 'b' region; the 'disordered' region; a UniProt-annotated variant site (in hema)

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.Pro947Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro947ser (accessed [today's date]).

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