Is NFIB p.Pro109= (c.327C>T) pathogenic?

NFIB p.Pro109= (c.327C>T) is classified Likely benign in NFIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-30). Very rare (popmax 0.00223%, eas); Associated with NFIB-related disorder.

What condition is associated with NFIB p.Pro109= (c.327C>T)?

NFIB p.Pro109= (c.327C>T) is associated with NFIB-related disorder (ClinVar).

How common is NFIB p.Pro109= (c.327C>T) in the general population?

NFIB p.Pro109= (c.327C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NFIB p.Pro109=

c.327C>T · rs202070696 · VCV3037612

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

NFIB-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 -0.51	GERP -5, phastCons 0.001
Overall
CADD	13.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,832 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,613,860 alleles · very rare exomes 17/1,461,888 · genomes 3/151,972 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,832
European (non-Finnish)	0.00153%	65,557
African / African-American	0.00134%	74,874

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: NFIB
Protein: p.Pro109=
Coding: c.327C>T
MANE Select: NM_001190737
dbSNP: rs202070696
Type: single nucleotide variant
Location: chr9:14307224 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 2 PDB
Residue 109: a DNA-binding region; a UniProt-annotated variant site (in macid)

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

Disease context

NFIB-related disorder

Similar variants

NFIB c.1385-2A>G Likely pathogenic ★ same condition
NFIB c.807-1G>A Likely pathogenic ★ same condition
NFIB p.Gln341Ter Likely pathogenic ★ same condition
NFIB p.Lys139Thr Likely pathogenic ★ same condition
NFIB p.Asp131Gly Uncertain significance ★ ⚠ same condition
NFIB p.Ser7Cys Uncertain significance ★ same condition
NFIB p.Val475Met Uncertain significance ★ same condition
NFIB p.Gly420Asp 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/nfib-p-pro109 (accessed [today's date]).

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