Is RECQL4 p.Pro1083= (c.3249C>T) pathogenic?

RECQL4 p.Pro1083= (c.3249C>T) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-30). Ultra-rare (popmax 0.0165%, mid); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro1083= (c.3249C>T)?

RECQL4 p.Pro1083= (c.3249C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro1083= (c.3249C>T) in the general population?

RECQL4 p.Pro1083= (c.3249C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RECQL4 p.Pro1083=

c.3249C>T · rs886038539 · VCV259259

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 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 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	GERP -0.48, phastCons 1
Overall
CADD	7.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000444%

Overall 0.00056% 9/1,608,278 alleles · ultra-rare exomes 9/1,455,954 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.00482%	20,756
South Asian	0.00332%	30,156
European (non-Finnish)	0.00017%	589,352

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.Pro1083=
Coding: c.3249C>T
MANE Select: NM_004260
dbSNP: rs886038539
Type: single nucleotide variant
Location: chr8:144512055 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 1083: a β-strand; 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.Pro1083Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro1083Thr Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro1083His Uncertain significance ★ ⚠ 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
RECQL4 c.1704+2T>G 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-pro1083 (accessed [today's date]).

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