Is F12 p.Ser115= (c.345C>T) pathogenic?

F12 p.Ser115= (c.345C>T) is classified Likely benign in F12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-20). Very rare (popmax 0.00549%, sas); Associated with F12-related disorder.

What condition is associated with F12 p.Ser115= (c.345C>T)?

F12 p.Ser115= (c.345C>T) is associated with F12-related disorder (ClinVar).

How common is F12 p.Ser115= (c.345C>T) in the general population?

F12 p.Ser115= (c.345C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

F12 p.Ser115=

c.345C>T · rs769220140 · VCV3043040

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

F12-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.3
Overall
CADD	0.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,086 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00161% 26/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
European (non-Finnish)	0.00169%	59,001
African / African-American	0.00133%	74,938

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: F12
Protein: p.Ser115=
Coding: c.345C>T
MANE Select: NM_000505
dbSNP: rs769220140
Type: single nucleotide variant
Location: chr5:177405375 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.47 · 17 PDB
Residue 115: a disulfide bond; the egf-like 1 domain

Full F12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F12-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F12 p.Gly561Arg Likely pathogenic ★ same condition
F12 c.1681-1G>A Conflicting classifications of pathogenicity ★ same condition
F12 p.Glu24Gly Uncertain significance ★ ⚠ same condition
F12 p.Thr37= Uncertain significance ★ same condition
F12 p.Arg226Leu Uncertain significance ⚠ same condition
F12 p.Gly8= Likely benign same condition
F12 c.1251-5del Likely benign same condition
F12 p.Glu193Ter Pathogenic/Likely 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/f12-p-ser115 (accessed [today's date]).

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