Is NFIX p.Met1Val (c.1A>G) pathogenic?

NFIX p.Met1Val (c.1A>G) is classified Uncertain significance in NFIX (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-24). No allele count reported in gnomAD v4.1 (AN 994,996).

How common is NFIX p.Met1Val (c.1A>G) in the general population?

NFIX p.Met1Val (c.1A>G) is no allele count reported in gnomAD v4.1 (AN 994,996) (gnomAD).

NFIX p.Met1Val

c.1A>G · rs2145117323 · VCV1309974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 994,996)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
REVEL	0.252	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.5	GERP 0.36, phastCons 1
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 994,996). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NFIX
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_001365902
dbSNP: rs2145117323
Type: single nucleotide variant
Location: chr19:12995838 (GRCh38)
Gene constraint: LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 62.94 · 3 PDB
Residue 1: a DNA-binding region

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

Similar variants

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
NFIX p.Arg116Gln Pathogenic/Likely pathogenic ★★ same type
NFIX p.Arg116Trp 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-met1val (accessed [today's date]).

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