Is RECQL4 p.Pro591Ser (c.1771C>T) pathogenic?

RECQL4 p.Pro591Ser (c.1771C>T) is classified Conflicting classifications of pathogenicity in RECQL4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-22). AlphaMissense: likely benign (0.0891); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Pro591Ser (c.1771C>T)?

RECQL4 p.Pro591Ser (c.1771C>T) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro591Ser (c.1771C>T) in the general population?

RECQL4 p.Pro591Ser (c.1771C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about RECQL4 p.Pro591Ser (c.1771C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro591Ser

c.1771C>T · rs909777665 · VCV945689

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
SaProt	LLR -14.24	damaging
⇒ SaProt calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3.1, phastCons 0.69
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	8.105	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,060 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000559% 9/1,611,046 alleles · very rare exomes 8/1,458,892 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,212
Remaining individualsnot grpmax-eligible	0.0016%	62,350
European (non-Finnish)	0.000254%	393,117

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.Pro591Ser
Coding: c.1771C>T
MANE Select: NM_004260
dbSNP: rs909777665
Type: single nucleotide variant
Location: chr8:144514296 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 591: the helicase atp-binding domain; a UniProt-annotated variant site (in)

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.Pro591Leu Benign ★★ ⚠ same residue
RECQL4 p.Pro591Arg Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro591His Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro591Thr Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro591fs 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

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-pro591ser (accessed [today's date]).

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