Is GTF2F2 p.Val84Phe (c.250G>T) pathogenic?

GTF2F2 p.Val84Phe (c.250G>T) is classified Uncertain significance in GTF2F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1224); Absent from gnomAD v4.1.

How common is GTF2F2 p.Val84Phe (c.250G>T) in the general population?

GTF2F2 p.Val84Phe (c.250G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GTF2F2 p.Val84Phe (c.250G>T)?

AlphaMissense predicts likely benign (score 0.1224) — an in-silico prediction, not a clinical call.

GTF2F2 p.Val84Phe

c.250G>T · VCV3523209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1224 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1224	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -8.03	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 7.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 163 kb · p 0.12 · regional, not allelic
Overall
CADD	19.72	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: GTF2F2
Protein: p.Val84Phe
Coding: c.250G>T
MANE Select: NM_004128
Type: single nucleotide variant
Location: chr13:45151777 (GRCh38)
Gene constraint: LOEUF 1.94 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 82.92 · 63 PDB
Residue 84: a β-strand

Full GTF2F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GTF2F2 p.Ala178Gly Uncertain significance ★ ⚠ same type
GTF2F2 p.Arg177Leu Uncertain significance ★ ⚠ same type
GTF2F2 p.Arg44Gln Uncertain significance ★ ⚠ same type
GTF2F2 p.Arg44Trp Uncertain significance ★ ⚠ same type
GTF2F2 p.Arg51Lys Uncertain significance ★ ⚠ same type
GTF2F2 p.Asn158Ser Uncertain significance ★ ⚠ same type
GTF2F2 p.Asp185Asn Uncertain significance ★ ⚠ same type
GTF2F2 p.Asp204Val Uncertain significance ★ 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/gtf2f2-p-val84phe (accessed [today's date]).

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