Is RECQL4 p.Pro147Ser (c.439C>T) pathogenic?

RECQL4 p.Pro147Ser (c.439C>T) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-08). AlphaMissense: likely benign (0.073); Very rare (popmax 0.00224%, eas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro147Ser (c.439C>T)?

RECQL4 p.Pro147Ser (c.439C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro147Ser (c.439C>T) in the general population?

RECQL4 p.Pro147Ser (c.439C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about RECQL4 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro147Ser

c.439C>T · rs2130728873 · VCV2021768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -2.1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	1.678	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,580 alleles

Overall 6.33e-05% 1/1,580,220 alleles · very rare exomes 1/1,427,910 · genomes 0/152,310 · joint denominator

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.Pro147Ser
Coding: c.439C>T
MANE Select: NM_004260
dbSNP: rs2130728873
Type: single nucleotide variant
Location: chr8:144516680 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 147: the 'disordered' region

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Baller-Gerold syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Pro147Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro147= Likely benign ★ 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
RECQL4 c.1705-1G>A 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-pro147ser (accessed [today's date]).

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