Is RECQL4 p.Pro591fs (c.1770_1807del) pathogenic?

RECQL4 p.Pro591fs (c.17701807del) is classified Pathogenic in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Very rare (popmax 0.00223%, eas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro591fs (c.1770_1807del)?

RECQL4 p.Pro591fs (c.1770_1807del) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro591fs (c.1770_1807del) in the general population?

RECQL4 p.Pro591fs (c.1770_1807del) is very rare (popmax 0.00223%, eas) (gnomAD).

RECQL4 p.Pro591fs

c.1770_1807del · rs780542343 · VCV575425

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 11 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 0.000124% 2/1,612,210 alleles · very rare exomes 2/1,459,942 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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.Pro591fs
Coding: c.1770_1807del
MANE Select: NM_004260
dbSNP: rs780542343
Type: Deletion
Location: chr8:144514260 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 591: the helicase atp-binding domain; a UniProt-annotated variant site (in)

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.Pro591Leu Benign ★★ ⚠ same residue
RECQL4 p.Pro591Arg Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro591His Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro591Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Pro591Thr Uncertain significance ★ ⚠ same residue
RECQL4 c.1131_1131+3del Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1390+2del Pathogenic ★★ same condition
RECQL4 c.359_374delGACCAGCCCTGGGCCG 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/recql4-p-pro591fs (accessed [today's date]).

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