Is HSF4 p.Pro429Thr (c.1285C>A) pathogenic?

HSF4 p.Pro429Thr (c.1285C>A) is classified Likely benign in HSF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.0484); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HSF4 p.Pro429Thr (c.1285C>A)?

HSF4 p.Pro429Thr (c.1285C>A) is associated with Inborn genetic diseases (ClinVar).

How common is HSF4 p.Pro429Thr (c.1285C>A) in the general population?

HSF4 p.Pro429Thr (c.1285C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HSF4 p.Pro429Thr (c.1285C>A)?

AlphaMissense predicts likely benign (score 0.0484) — an in-silico prediction, not a clinical call.

HSF4 p.Pro429Thr

c.1285C>A · VCV4272471

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0484 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0484	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.06	GERP -3.3
Regional constraint	o/e 0.94	unconstrained · MANE · 4,970 bp · p 0.11 · regional, not allelic
Overall
CADD	7.035	PHRED · no single calibrated threshold — expert panels disagree

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: HSF4
Protein: p.Pro429Thr
Coding: c.1285C>A
MANE Select: NM_001374675
Type: single nucleotide variant
Location: chr16:67169309 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HSF4 p.Ala320Gly Uncertain significance ★★ ⚠ same condition
HSF4 p.Ala432Val Uncertain significance ★★ ⚠ same condition
HSF4 p.Glu115Gly Uncertain significance ★★ ⚠ same condition
HSF4 p.Gly13Asp Uncertain significance ★★ ⚠ same condition
HSF4 p.Gly442Glu Uncertain significance ★★ ⚠ same condition
HSF4 p.Ile86Thr Uncertain significance ★★ ⚠ same condition
HSF4 p.Met68Thr Uncertain significance ★★ ⚠ same condition
HSF4 p.Ser269Phe Uncertain significance ★★ ⚠ 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-pro429thr (accessed [today's date]).

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