Is F11 p.Ser575Leu (c.1724C>T) pathogenic?

F11 p.Ser575Leu (c.1724C>T) is classified Likely pathogenic in F11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-14). AlphaMissense: likely pathogenic (0.7974); Very rare (popmax 0.00267%, afr); Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Ser575Leu (c.1724C>T)?

F11 p.Ser575Leu (c.1724C>T) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Ser575Leu (c.1724C>T) in the general population?

F11 p.Ser575Leu (c.1724C>T) is very rare (popmax 0.00267%, afr) (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.Ser575Leu (c.1724C>T)?

AlphaMissense predicts likely pathogenic (score 0.7974) — an in-silico prediction, not a clinical call.

F11 p.Ser575Leu

c.1724C>T · rs281875250 · VCV68187

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7974 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.7974	likely pathogenic ✓ concordant with ClinVar
REVEL	0.884	moderately pathogenic-leaning
SaProt	LLR -12.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.2	GERP 1.5, phastCons 1
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,902 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,613,912 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,451
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000254%	393,323

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.Ser575Leu
Coding: c.1724C>T
dbSNP: rs281875250
Type: single nucleotide variant
Location: chr4:186288460 (GRCh38)

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)

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-ser575leu (accessed [today's date]).

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