Is RECQL4 p.Arg623= (c.1869C>G) pathogenic?

RECQL4 p.Arg623= (c.1869C>G) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-01). Very rare (popmax 0.00668%, afr); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Arg623= (c.1869C>G)?

RECQL4 p.Arg623= (c.1869C>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg623= (c.1869C>G) in the general population?

RECQL4 p.Arg623= (c.1869C>G) is very rare (popmax 0.00668%, afr) (gnomAD).

RECQL4 p.Arg623=

c.1869C>G · rs368736533 · VCV1145055

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

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 -7.3	GERP -3.2
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,862 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000496% 8/1,612,124 alleles · very rare exomes 2/1,460,106 · genomes 6/152,018 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,972
Admixed American	0.00167%	59,964
European (non-Finnish)	0.00017%	589,859

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.Arg623=
Coding: c.1869C>G
MANE Select: NM_004260
dbSNP: rs368736533
Type: single nucleotide variant
Location: chr8:144514198 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 623: 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.Arg623Cys Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg623Gly Uncertain significance ★ same residue
RECQL4 p.Arg623His Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Arg623Pro 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

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-arg623 (accessed [today's date]).

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