Is F11 p.Thr593= (c.1779G>A) pathogenic?

F11 p.Thr593= (c.1779G>A) is classified Likely benign in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-29). Very rare (popmax 0.0022%, sas).

How common is F11 p.Thr593= (c.1779G>A) in the general population?

F11 p.Thr593= (c.1779G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

F11 p.Thr593=

c.1779G>A · rs2126791307 · VCV1143417

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.044	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.7
Overall
CADD	0.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000547% 8/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
Finnishnot grpmax-eligible	0.00156%	64,034
European (non-Finnish)	0.000424%	236,008

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.Thr593=
Coding: c.1779G>A
MANE Select: NM_000128
dbSNP: rs2126791307
Type: single nucleotide variant
Location: chr4:186288515 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 593: a β-strand; a disulfide bond; the peptidase s1 domain

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

Similar variants

F11 p.Thr593Met Pathogenic/Likely pathogenic ★★ ⚠ same residue
F11 p.Thr593Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
F11 p.Thr593Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
F11 c.1136-1G>C Likely pathogenic ★★ same type
F11 c.1480+1G>T Likely pathogenic ★★ same type
F11 c.1481-1G>T Likely pathogenic ★★ same type
F11 c.1716+1G>A Pathogenic ★★ same type
F11 c.325+1G>A Pathogenic ★★ same type

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-thr593 (accessed [today's date]).

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