Is F5 p.Thr642= (c.1926C>A) pathogenic?

F5 p.Thr642= (c.1926C>A) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with thrombophilia due to thrombin defect.

What condition is associated with F5 p.Thr642= (c.1926C>A)?

F5 p.Thr642= (c.1926C>A) is associated with thrombophilia due to thrombin defect, congenital factor V deficiency, Budd-Chiari syndrome (ClinVar).

F5 p.Thr642=

Q: How common is F5 p.Thr642= (c.1926C>A) in the general population?

F5 p.Thr642= (c.1926C>A) is common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1926C>A · rs6037 · VCV255192

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

thrombophilia due to thrombin defect

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.26	GERP -0.93, phastCons 0.92
Overall
CADD	5.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.4% Admixed American · 6,226/59,996 alleles

Filtering AF 10.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.1%

Overall 7.28% 117,475/1,613,708 alleles · common exomes 107,744/1,461,566 · genomes 9,731/152,142 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	11.2%	9
Admixed Americangrpmax	10.4%	10
Middle Eastern	9.62%	10
South Asian	8.34%	12
Remaining individualsnot grpmax-eligible	7.31%	14
European (non-Finnish)	7.3%	14
Ashkenazi Jewishnot grpmax-eligible	7.25%	14
East Asian	4.77%	21
Amishnot grpmax-eligible	1.54%	65
African / African-American	1.19%	84

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: F5
Protein: p.Thr642=
Coding: c.1926C>A
MANE Select: NM_000130
dbSNP: rs6037
Type: single nucleotide variant
Location: chr1:169544345 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 642: the plastocyanin-like 4 domain; a β-strand; the f5/8 type a 2 domain

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

thrombophilia due to thrombin defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital factor V deficiency Budd-Chiari syndrome factor V deficiency

Similar variants

F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Asp96His 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/f5-p-thr642 (accessed [today's date]).

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