Is NFIX p.Thr96Arg (c.287C>G) pathogenic?

NFIX p.Thr96Arg (c.287C>G) is classified Uncertain significance in NFIX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). AlphaMissense: likely pathogenic (0.9775); Absent from gnomAD v4.1.

How common is NFIX p.Thr96Arg (c.287C>G) in the general population?

NFIX p.Thr96Arg (c.287C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NFIX p.Thr96Arg (c.287C>G)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

NFIX p.Thr96Arg

c.287C>G · rs2512744750 · VCV2649362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9775	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -14.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 29 kb · p 2.2e-11 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NFIX
Protein: p.Thr96Arg
Coding: c.287C>G
MANE Select: NM_001365902
dbSNP: rs2512744750
Type: single nucleotide variant
Location: chr19:13025280 (GRCh38)
Gene constraint: LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.94 · 3 PDB
Residue 96: a DNA-binding region; an α-helix

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

Similar variants

NFIX p.Thr96= Likely benign ★★ same residue
NFIX p.Thr96_Pro100del Uncertain significance ★ same residue
NFIX c.559+1G>A Pathogenic ★★ same type
NFIX c.697+1G>A Pathogenic/Likely pathogenic ★★ same type
NFIX c.818+1G>A Likely pathogenic ★★ same type
NFIX c.955+1G>A Pathogenic ★★ same type
NFIX c.955+1G>T Pathogenic ★★ same type
NFIX p.Arg115Gln 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/nfix-p-thr96arg (accessed [today's date]).

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