Is F11 p.Phe30Ser (c.89T>C) pathogenic?

F11 p.Phe30Ser (c.89T>C) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.7394); Very rare (popmax 8.47e-05%, nfe); Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Phe30Ser (c.89T>C)?

F11 p.Phe30Ser (c.89T>C) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Phe30Ser (c.89T>C) in the general population?

F11 p.Phe30Ser (c.89T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Congenital factor XI deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F11 p.Phe30Ser (c.89T>C)?

AlphaMissense predicts likely pathogenic (score 0.7394) — an in-silico prediction, not a clinical call.

F11 p.Phe30Ser

c.89T>C · rs932824943 · VCV1703828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7394 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.7394	likely pathogenic
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -13.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.2e-05% 1/1,614,150 alleles · very rare exomes 1/1,461,870 · genomes 0/152,280 · 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: F11
Protein: p.Phe30Ser
Coding: c.89T>C
MANE Select: NM_000128
dbSNP: rs932824943
Type: single nucleotide variant
Location: chr4:186271642 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 30: a β-strand; the apple 1 domain; a UniProt-annotated variant site (in fa11d)

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Congenital factor XI deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F11 p.Phe30fs Likely pathogenic ★ same residue
F11 p.Phe30Cys Uncertain significance ⚠ same residue
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 c.865+2T>C 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/f11-p-phe30ser (accessed [today's date]).

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