Is NFIX p.Arg24= (c.72C>T) pathogenic?

NFIX p.Arg24= (c.72C>T) is classified Likely benign in NFIX (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-05). Very rare (popmax 0.00223%, eas); Associated with NFIX-related disorder.

What condition is associated with NFIX p.Arg24= (c.72C>T)?

NFIX p.Arg24= (c.72C>T) is associated with NFIX-related disorder (ClinVar).

How common is NFIX p.Arg24= (c.72C>T) in the general population?

NFIX p.Arg24= (c.72C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NFIX p.Arg24=

c.72C>T · rs368774795 · VCV3029907

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

NFIX-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.36	GERP -4.5, phastCons 0.98
Overall
CADD	13.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,613,924 alleles · very rare exomes 4/1,461,706 · genomes 1/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
South Asian	0.0022%	45,535
European (non-Finnish)	0.000169%	589,974

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.Arg24=
Coding: c.72C>T
MANE Select: NM_001365902
dbSNP: rs368774795
Type: single nucleotide variant
Location: chr19:13025065 (GRCh38)
Gene constraint: LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.94 · 3 PDB
Residue 24: a DNA-binding region

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

Disease context

NFIX-related disorder

Similar variants

NFIX c.955+1G>A Pathogenic ★★ same condition
NFIX p.Trp127Cys Likely pathogenic ★★ same condition
NFIX c.622+2T>G Likely pathogenic ★ same condition
NFIX p.Arg116Leu Likely pathogenic ★ same condition
NFIX p.Gln197Ter Pathogenic ★ same condition
NFIX p.Gln414Ter Pathogenic ★ same condition
NFIX p.Glu52Gln Likely pathogenic ★ ⚠ same condition
NFIX p.Glu89Ter Likely pathogenic ★ 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-arg24 (accessed [today's date]).

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