Is RECQL4 p.Arg1069Cys (c.3205C>T) pathogenic?

RECQL4 p.Arg1069Cys (c.3205C>T) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.0815); Ultra-rare (popmax 0.0473%, sas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Arg1069Cys (c.3205C>T)?

RECQL4 p.Arg1069Cys (c.3205C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg1069Cys (c.3205C>T) in the general population?

RECQL4 p.Arg1069Cys (c.3205C>T) is ultra-rare (popmax 0.0473%, sas) (gnomAD).

What do computational predictors say about RECQL4 p.Arg1069Cys (c.3205C>T)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

RECQL4 p.Arg1069Cys

c.3205C>T · rs758648484 · VCV528970

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0473%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -2.3, phastCons 0.001
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	9.751	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0473% South Asian · 43/90,990 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.00366% 59/1,611,256 alleles · ultra-rare exomes 58/1,459,012 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0473%	2,116
Remaining individualsnot grpmax-eligible	0.00481%	20,787
East Asian	0.00446%	22,437
Admixed American	0.00334%	29,950
European (non-Finnish)	0.000763%	131,041

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.Arg1069Cys
Coding: c.3205C>T
MANE Select: NM_004260
dbSNP: rs758648484
Type: single nucleotide variant
Location: chr8:144512175 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 1069: an α-helix; a UniProt-annotated variant site (in rts2)

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.Arg1069His Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg1069Gly Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg1069Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg1069Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg1069= Likely benign ★ 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

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-arg1069cys (accessed [today's date]).

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