Is F13B p.Arg645Ser (c.1935A>T) pathogenic?

F13B p.Arg645Ser (c.1935A>T) is classified Uncertain significance in F13B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-11). AlphaMissense: likely benign (0.1504); Rare (popmax 0.337%, afr); Associated with Inborn genetic diseases.

What condition is associated with F13B p.Arg645Ser (c.1935A>T)?

F13B p.Arg645Ser (c.1935A>T) is associated with Inborn genetic diseases, factor XIII, b subunit, deficiency of (ClinVar).

How common is F13B p.Arg645Ser (c.1935A>T) in the general population?

F13B p.Arg645Ser (c.1935A>T) is rare (popmax 0.337%, afr) (gnomAD).

What do computational predictors say about F13B p.Arg645Ser (c.1935A>T)?

AlphaMissense predicts likely benign (score 0.1504) — an in-silico prediction, not a clinical call.

F13B p.Arg645Ser

c.1935A>T · rs149091258 · VCV875613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1504 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.337%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1504	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.46	GERP -3.7
Regional constraint	o/e 0.99	unconstrained · MANE · 28 kb · p 0.89 · regional, not allelic
Overall
CADD	13.82	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

Grpmax group 0.337% African / African-American · 252/74,860 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.289%

Overall 0.0173% 278/1,610,296 alleles · rare exomes 136/1,458,364 · genomes 142/151,932 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.337%	297
Admixed American	0.0217%	4,611
Remaining individualsnot grpmax-eligible	0.0144%	6,926
European (non-Finnish)	0.00034%	294,364

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: F13B
Protein: p.Arg645Ser
Coding: c.1935A>T
MANE Select: NM_001994
dbSNP: rs149091258
Type: single nucleotide variant
Location: chr1:197040539 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.55 · 2 PDB
Residue 645: the sushi 10 domain

Full F13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: factor XIII, b subunit, deficiency of

Similar variants

F13B c.805+1G>A Likely pathogenic ★★ same condition
F13B c.986-4T>C Uncertain significance ★★ same condition
F13B p.Ala363= Uncertain significance ★★ same condition
F13B p.Arg293Cys Uncertain significance ★★ ⚠ same condition
F13B p.Arg315Cys Uncertain significance ★★ ⚠ same condition
F13B p.His225Gln Uncertain significance ★★ ⚠ same condition
F13B p.His557Arg Uncertain significance ★★ ⚠ same condition
F13B p.Tyr354His 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/f13b-p-arg645ser (accessed [today's date]).

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