Is RECQL4 p.Arg647= (c.1941C>T) pathogenic?

RECQL4 p.Arg647= (c.1941C>T) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-30). Very rare (popmax 0.00468%, eas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Arg647= (c.1941C>T)?

RECQL4 p.Arg647= (c.1941C>T) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg647= (c.1941C>T) in the general population?

RECQL4 p.Arg647= (c.1941C>T) is very rare (popmax 0.00468%, eas) (gnomAD).

RECQL4 p.Arg647=

c.1941C>T · rs780721989 · VCV1111491

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00468%, eas)

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 5.9	GERP 0.59, phastCons 1
Overall
CADD	7.949	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00468% East Asian · 2/42,762 alleles

Filtering AF 0.000775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00029%

Overall 0.000316% 5/1,579,846 alleles · very rare exomes 5/1,427,644 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00468%	21,381
European (non-Finnish)	0.000258%	388,007

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.Arg647=
Coding: c.1941C>T
MANE Select: NM_004260
dbSNP: rs780721989
Type: single nucleotide variant
Location: chr8:144514045 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 647: the helicase atp-binding domain; an α-helix

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.Arg647Cys Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg647Gly Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg647His Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg647Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg647Pro Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg647Ser Likely benign ★ 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-arg647 (accessed [today's date]).

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