Is FGB p.Ser371= (c.1113A>G) pathogenic?

FGB p.Ser371= (c.1113A>G) is classified Benign/Likely benign in FGB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Rare (popmax 0.342%, nfe); Associated with congenital afibrinogenemia.

What condition is associated with FGB p.Ser371= (c.1113A>G)?

FGB p.Ser371= (c.1113A>G) is associated with congenital afibrinogenemia (ClinVar).

How common is FGB p.Ser371= (c.1113A>G) in the general population?

FGB p.Ser371= (c.1113A>G) is rare (popmax 0.342%, nfe) (gnomAD).

FGB p.Ser371=

c.1113A>G · rs6057 · VCV347775

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.342%, nfe)

Conditions

congenital afibrinogenemia

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 -5.7	GERP -5.7
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.342% European (non-Finnish) · 4,034/1,180,004 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.329%

Overall 0.404% 6,518/1,614,152 alleles · rare exomes 5,690/1,461,840 · genomes 828/152,312 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.21%	31
European (non-Finnish)grpmax	0.342%	293
Remaining individualsnot grpmax-eligible	0.314%	319
Ashkenazi Jewishnot grpmax-eligible	0.297%	336
Admixed American	0.143%	698
Middle Eastern	0.0495%	2,021
South Asian	0.0384%	2,602
African / African-American	0.024%	4,169

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: FGB
Protein: p.Ser371=
Coding: c.1113A>G
MANE Select: NM_005141
dbSNP: rs6057
Type: single nucleotide variant
Location: chr4:154569668 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 84.43 · 41 PDB
Residue 371: the fibrinogen c-terminal domain; a β-strand

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

Disease context

congenital afibrinogenemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGB p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
FGB p.Arg74Leu Uncertain significance ★★ same condition
FGB p.Asp35Asn Uncertain significance ★★ ⚠ same condition
FGB p.Gln219Arg Uncertain significance ★★ ⚠ same condition
FGB p.Glu250Gly Uncertain significance ★★ ⚠ same condition
FGB p.Leu27Pro Uncertain significance ★★ ⚠ same condition
FGB p.Lys2Glu Uncertain significance ★★ ⚠ same condition
FGB p.Lys84Thr 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/fgb-p-ser371 (accessed [today's date]).

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