Is RECQL4 p.Arg263= (c.789A>G) pathogenic?

RECQL4 p.Arg263= (c.789A>G) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Arg263= (c.789A>G)?

RECQL4 p.Arg263= (c.789A>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg263= (c.789A>G) in the general population?

RECQL4 p.Arg263= (c.789A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

RECQL4 p.Arg263=

c.789A>G · rs1430320264 · VCV699181

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.6	GERP -3.3
Overall
CADD	0.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000559% 9/1,609,518 alleles · ultra-rare exomes 7/1,457,364 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0033%	30,301
Remaining individualsnot grpmax-eligible	0.0016%	62,400
European (non-Finnish)	0.000339%	294,852

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.Arg263=
Coding: c.789A>G
MANE Select: NM_004260
dbSNP: rs1430320264
Type: single nucleotide variant
Location: chr8:144516330 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 263: the 'disordered' region

Full RECQL4 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

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Arg263Lys Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg263Gly Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg263Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg263_Trp264insTer Pathogenic ★★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1391-1G>A Pathogenic ★★ same condition
RECQL4 c.1704+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-arg263 (accessed [today's date]).

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