Is RECQL4 p.Ala587= (c.1761G>A) pathogenic?

RECQL4 p.Ala587= (c.1761G>A) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-20). Ultra-rare (popmax 0.0165%, mid); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ala587= (c.1761G>A)?

RECQL4 p.Ala587= (c.1761G>A) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ala587= (c.1761G>A) in the general population?

RECQL4 p.Ala587= (c.1761G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RECQL4 p.Ala587=

c.1761G>A · rs777920456 · VCV697258

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,050 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00255% 41/1,610,022 alleles · ultra-rare exomes 31/1,457,752 · genomes 10/152,270 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,050
African / African-American	0.00934%	10,712
Admixed American	0.00835%	11,973
South Asian	0.0033%	30,334
Remaining individualsnot grpmax-eligible	0.00321%	31,157
European (non-Finnish)	0.00195%	51,249

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.Ala587=
Coding: c.1761G>A
MANE Select: NM_004260
dbSNP: rs777920456
Type: single nucleotide variant
Location: chr8:144514306 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 587: the helicase atp-binding domain; a β-strand

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.Ala587Pro Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala587Thr Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala587Glu Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala587Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala587Val Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala587fs Pathogenic ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A 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-ala587 (accessed [today's date]).

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