Is NFIB p.Pro363Ser (c.1087C>T) pathogenic?

NFIB p.Pro363Ser (c.1087C>T) is classified Uncertain significance in NFIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.0624); Very rare (popmax 0.00402%, afr); Associated with Inborn genetic diseases.

What condition is associated with NFIB p.Pro363Ser (c.1087C>T)?

NFIB p.Pro363Ser (c.1087C>T) is associated with Inborn genetic diseases (ClinVar).

How common is NFIB p.Pro363Ser (c.1087C>T) in the general population?

NFIB p.Pro363Ser (c.1087C>T) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about NFIB p.Pro363Ser (c.1087C>T)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

NFIB p.Pro363Ser

c.1087C>T · rs749973345 · VCV3197510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	24.8	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 0.00402% African / African-American · 3/74,690 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000248% 4/1,611,206 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,897
Remaining individualsnot grpmax-eligible	0.0016%	62,368

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.Pro363Ser
Coding: c.1087C>T
MANE Select: NM_001190737
dbSNP: rs749973345
Type: single nucleotide variant
Location: chr9:14120598 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 2 PDB
Residue 363: a UniProt-annotated variant site (in macid); the 'disordered' region

Full NFIB 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

Similar variants

NFIB p.Asp309Val Uncertain significance ★★ ⚠ same condition
NFIB p.Glu305Gln Uncertain significance ★★ ⚠ same condition
NFIB p.Pro329Ser Uncertain significance ★★ ⚠ same condition
NFIB c.1061-1G>C Likely pathogenic ★ same condition
NFIB c.806+3A>C Uncertain significance ★ same condition
NFIB p.Arg81Cys Uncertain significance ★ ⚠ same condition
NFIB p.Asn219Asp Uncertain significance ★ ⚠ same condition
NFIB p.Asn219Ser 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-pro363ser (accessed [today's date]).

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