Is HSF4 p.Glu3Ter (c.7G>T) pathogenic?

HSF4 p.Glu3Ter (c.7G>T) is classified Likely pathogenic in HSF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Absent from gnomAD v4.1; Associated with HSF4-related disorder.

What condition is associated with HSF4 p.Glu3Ter (c.7G>T)?

HSF4 p.Glu3Ter (c.7G>T) is associated with HSF4-related disorder (ClinVar).

How common is HSF4 p.Glu3Ter (c.7G>T) in the general population?

HSF4 p.Glu3Ter (c.7G>T) is absent from gnomAD v4.1 (gnomAD).

HSF4 p.Glu3Ter

c.7G>T · rs2031121154 · VCV2636293

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,034)

Conditions

HSF4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 13
Splicing
SpliceAI	Δ0.56	donor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Overall
CADD	39.0	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 1,600,034). 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: HSF4
Protein: p.Glu3Ter
Coding: c.7G>T
MANE Select: NM_001374675
dbSNP: rs2031121154
Type: single nucleotide variant
Location: chr16:67164818 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.04 · 2 PDB

Full HSF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HSF4-related disorder

Similar variants

HSF4 p.Glu3Gly Uncertain significance ★★ ⚠ same residue
HSF4 p.Arg119Cys Pathogenic ★ same condition
HSF4 p.Gln112Ter Likely pathogenic ★ same condition
HSF4 c.562-1G>C Uncertain significance ★ same condition
HSF4 p.Leu136Val Uncertain significance ★ ⚠ same condition
HSF4 p.Arg118Gly Uncertain significance ⚠ same condition
HSF4 p.Tyr78Ser Uncertain significance ⚠ same condition
HSF4 p.Arg405= Likely benign 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/hsf4-p-glu3ter (accessed [today's date]).

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