Is RECQL4 p.Ala653= (c.1959A>G) pathogenic?

RECQL4 p.Ala653= (c.1959A>G) is classified Benign/Likely benign in RECQL4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Rare (popmax 0.247%, eas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Ala653= (c.1959A>G)?

RECQL4 p.Ala653= (c.1959A>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ala653= (c.1959A>G) in the general population?

RECQL4 p.Ala653= (c.1959A>G) is rare (popmax 0.247%, eas) (gnomAD).

RECQL4 p.Ala653=

c.1959A>G · rs574411332 · VCV239712

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, eas)

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 1.5	GERP -3.5, phastCons 0.98
Overall
CADD	5.713	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% East Asian · 105/42,466 alleles

Filtering AF 0.209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.00699% 110/1,574,384 alleles · rare exomes 101/1,422,232 · genomes 9/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.247%	404
Remaining individualsnot grpmax-eligible	0.00655%	15,261
Admixed American	0.00185%	54,190

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.Ala653=
Coding: c.1959A>G
MANE Select: NM_004260
dbSNP: rs574411332
Type: single nucleotide variant
Location: chr8:144514027 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 653: 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.Ala653Val Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ala653Glu Uncertain significance ★ same residue
RECQL4 p.Ala653Gly Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala653Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala653Thr 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

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-ala653 (accessed [today's date]).

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