Is F10 p.Leu10Phe (c.28C>T) pathogenic?

F10 p.Leu10Phe (c.28C>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-28). AlphaMissense: likely benign (0.0821); Absent from gnomAD v4.1; Associated with factor X deficiency.

What condition is associated with F10 p.Leu10Phe (c.28C>T)?

F10 p.Leu10Phe (c.28C>T) is associated with factor X deficiency (ClinVar).

How common is F10 p.Leu10Phe (c.28C>T) in the general population?

F10 p.Leu10Phe (c.28C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F10 p.Leu10Phe (c.28C>T)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

F10 p.Leu10Phe

c.28C>T · rs2142244681 · VCV1098451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -8.62	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 1.9	GERP 0.16, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 17 kb · p 0.36 · regional, not allelic
Overall
CADD	21.5	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: F10
Protein: p.Leu10Phe
Coding: c.28C>T
MANE Select: NM_000504
dbSNP: rs2142244681
Type: single nucleotide variant
Location: chr13:113122883 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB

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

Similar variants

F10 p.Leu10= Likely benign ★ same residue
F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly21Arg Pathogenic ★★ ⚠ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu69Lys Likely pathogenic ★ same condition
F10 p.Thr358Met Likely pathogenic ★ ⚠ same condition
F10 p.Arg27His Uncertain significance ★ ⚠ same condition
F10 p.Asp463His 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/f10-p-leu10phe (accessed [today's date]).

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