Is NFIB p.Val237Phe (c.709G>T) pathogenic?

NFIB p.Val237Phe (c.709G>T) is classified Uncertain significance in NFIB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1116); Absent from gnomAD v4.1; Associated with macrocephaly, acquired, with impaired intellectual development.

What condition is associated with NFIB p.Val237Phe (c.709G>T)?

NFIB p.Val237Phe (c.709G>T) is associated with macrocephaly, acquired, with impaired intellectual development (ClinVar).

How common is NFIB p.Val237Phe (c.709G>T) in the general population?

NFIB p.Val237Phe (c.709G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NFIB p.Val237Phe (c.709G>T)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

NFIB p.Val237Phe

c.709G>T · VCV4079429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

macrocephaly, acquired, with impaired intellectual development

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: NFIB
Protein: p.Val237Phe
Coding: c.709G>T
MANE Select: NM_001190737
Type: single nucleotide variant
Location: chr9:14150242 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 2 PDB
Residue 237: a UniProt-annotated variant site (in macid)

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

Disease context

macrocephaly, acquired, with impaired intellectual development — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NFIB p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
NFIB p.Arg37Ter Pathogenic ★★ same condition
NFIB p.Arg39Cys Pathogenic/Likely pathogenic ★★ same condition
NFIB p.Arg48Ter Pathogenic/Likely pathogenic ★★ same condition
NFIB p.Arg89Ter Pathogenic/Likely pathogenic ★★ same condition
NFIB p.Gln123Ter Likely pathogenic ★★ same condition
NFIB p.Leu132Pro Pathogenic/Likely pathogenic ★★ same condition
NFIB p.Lys126Glu Pathogenic/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/nfib-p-val237phe (accessed [today's date]).

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