Is RECQL4 p.Pro545= (c.1635A>G) pathogenic?

RECQL4 p.Pro545= (c.1635A>G) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-07). Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Pro545= (c.1635A>G)?

RECQL4 p.Pro545= (c.1635A>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro545= (c.1635A>G) in the general population?

RECQL4 p.Pro545= (c.1635A>G) is very rare (popmax 0.004%, afr) (gnomAD).

RECQL4 p.Pro545=

c.1635A>G · rs563366558 · VCV1093407

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -3.6, phastCons 0.007
Overall
CADD	2.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,978 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,611,526 alleles · very rare exomes 6/1,459,340 · genomes 0/152,186 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00481%	20,811
African / African-Americangrpmax	0.004%	24,993

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro545=
Coding: c.1635A>G
MANE Select: NM_004260
dbSNP: rs563366558
Type: single nucleotide variant
Location: chr8:144514511 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 545: the helicase atp-binding domain; a turn

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.Pro545Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro545Ser Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro545fs 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
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-pro545 (accessed [today's date]).

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