Is NFIX p.Pro382Gln (c.1145C>A) pathogenic?

NFIX p.Pro382Gln (c.1145C>A) is classified Uncertain significance in NFIX (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-12). AlphaMissense: ambiguous (0.4); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NFIX p.Pro382Gln (c.1145C>A)?

NFIX p.Pro382Gln (c.1145C>A) is associated with Inborn genetic diseases (ClinVar).

How common is NFIX p.Pro382Gln (c.1145C>A) in the general population?

NFIX p.Pro382Gln (c.1145C>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about NFIX p.Pro382Gln (c.1145C>A)?

AlphaMissense predicts ambiguous (score 0.4) — an in-silico prediction, not a clinical call.

NFIX p.Pro382Gln

c.1145C>A · VCV4861041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4	ambiguous
REVEL	0.286	benign-leaning
SaProt	LLR -10.08	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.30	constrained · MANE · 6,378 bp · p 9.4e-14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,886 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,970 alleles · very rare exomes 5/1,461,674 · genomes 0/152,296 · joint denominator

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: NFIX
Protein: p.Pro382Gln
Coding: c.1145C>A
MANE Select: NM_001365902
Type: single nucleotide variant
Location: chr19:13081746 (GRCh38)
Gene constraint: LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.94 · 3 PDB

Full NFIX 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

NFIX p.Pro382Leu Uncertain significance ★ ⚠ same residue
NFIX p.Pro382= Likely benign ★ same residue
NFIX c.559+1G>A Pathogenic ★★ same condition
NFIX p.Glu52Ter Pathogenic/Likely pathogenic ★★ same condition
NFIX p.Leu120Arg Uncertain significance ★★ ⚠ same condition
NFIX p.Leu261Met Uncertain significance ★★ ⚠ same condition
NFIX p.Ile202Val Likely benign ★★ same condition
NFIX c.28-16G>A Conflicting classifications of pathogenicity ★ 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/nfix-p-pro382gln (accessed [today's date]).

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