Is NFIX p.Val230fs (c.687_688dup) pathogenic?

NFIX p.Val230fs (c.687688dup) is classified Pathogenic in NFIX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). No gnomAD frequency available for this variant; Associated with Malan overgrowth syndrome.

What condition is associated with NFIX p.Val230fs (c.687_688dup)?

NFIX p.Val230fs (c.687_688dup) is associated with Malan overgrowth syndrome, Marshall-Smith syndrome (ClinVar).

How common is NFIX p.Val230fs (c.687_688dup) in the general population?

NFIX p.Val230fs (c.687_688dup) is no gnomAD frequency available for this variant (gnomAD).

NFIX p.Val230fs

c.687_688dup · rs2512941801 · VCV2068227

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Malan overgrowth syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val230fs
Coding: c.687_688dup
MANE Select: NM_001365902
dbSNP: rs2512941801
Type: Microsatellite
Location: chr19:13073482 (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

Malan overgrowth syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Marshall-Smith syndrome

Similar variants

NFIX p.Val230= Likely benign ★ same residue
NFIX p.His395_Gly396insHis Likely benign ★★ same condition
NFIX c.28-340GT[6] Uncertain significance ★ same condition
NFIX p.Gln338fs Pathogenic same condition
NFIX p.Ser337fs Pathogenic same condition
NFIX c.697+1G>A Pathogenic/Likely pathogenic ★★ same condition
NFIX c.818+1G>A Likely pathogenic ★★ same condition
NFIX c.955+1G>A 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-val230fs (accessed [today's date]).

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