Is F10 p.Arg28Ser (c.84G>T) pathogenic?

F10 p.Arg28Ser (c.84G>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely benign (0.2461); Very rare (popmax 0.00133%, afr); Associated with factor X deficiency.

What condition is associated with F10 p.Arg28Ser (c.84G>T)?

F10 p.Arg28Ser (c.84G>T) is associated with factor X deficiency (ClinVar).

How common is F10 p.Arg28Ser (c.84G>T) in the general population?

F10 p.Arg28Ser (c.84G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about F10 p.Arg28Ser (c.84G>T)?

AlphaMissense predicts likely benign (score 0.2461) — an in-silico prediction, not a clinical call.

F10 p.Arg28Ser

c.84G>T · rs1212018525 · VCV1098480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.2461	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.056	GERP -3.8
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.36 · regional, not allelic
Overall
CADD	5.133	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 0.00133% African / African-American · 1/75,002 alleles

Overall 6.84e-05% 1/1,461,612 alleles · very rare

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: F10
Protein: p.Arg28Ser
Coding: c.84G>T
dbSNP: rs1212018525
Type: single nucleotide variant
Location: chr13:113129465 (GRCh38)

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor X deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/f10-p-arg28ser (accessed [today's date]).

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