Is RECQL4 p.Pro545fs (c.1631dup) pathogenic?

RECQL4 p.Pro545fs (c.1631dup) is classified Pathogenic in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). Very rare (popmax 6.21e-05%); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro545fs (c.1631dup)?

RECQL4 p.Pro545fs (c.1631dup) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro545fs (c.1631dup) in the general population?

RECQL4 p.Pro545fs (c.1631dup) is very rare (popmax 6.21e-05%) (gnomAD).

RECQL4 p.Pro545fs

c.1631dup · rs2130698955 · VCV1413788

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.21e-05%)

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.43	GERP -0.52, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.21e-05%

Overall 6.21e-05% 1/1,611,416 alleles · very rare exomes 1/1,459,142 · genomes 0/152,274 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RECQL4
Protein: p.Pro545fs
Coding: c.1631dup
MANE Select: NM_004260
dbSNP: rs2130698955
Type: Duplication
Location: chr8:144514514 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 545: the helicase atp-binding domain; a turn

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Baller-Gerold syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Pro545Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro545Ser Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro545= Likely benign ★★ same residue
RECQL4 p.Arg804fs Pathogenic ★★ same condition
RECQL4 p.Lys738fs Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1705-23_1705-7dup Uncertain significance ★★ same condition
RECQL4 c.2755+16dup Benign/Likely benign ★★ same condition
RECQL4 p.Ala571fs 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/recql4-p-pro545fs (accessed [today's date]).

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