Is RECQL4 p.Pro515Ser (c.1543C>T) pathogenic?

RECQL4 p.Pro515Ser (c.1543C>T) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-20). AlphaMissense: likely pathogenic (0.8002); Very rare (popmax 0.000678%, nfe); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro515Ser (c.1543C>T)?

RECQL4 p.Pro515Ser (c.1543C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro515Ser (c.1543C>T) in the general population?

RECQL4 p.Pro515Ser (c.1543C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about RECQL4 p.Pro515Ser (c.1543C>T)?

AlphaMissense predicts likely pathogenic (score 0.8002) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro515Ser

c.1543C>T · rs761310564 · VCV955367

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.8002	likely pathogenic · top 8% in RECQL4
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000678% European (non-Finnish) · 8/1,179,290 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000497% 8/1,610,854 alleles · very rare exomes 7/1,458,682 · genomes 1/152,172 · 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.Pro515Ser
Coding: c.1543C>T
MANE Select: NM_004260
dbSNP: rs761310564
Type: single nucleotide variant
Location: chr8:144515013 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 515: the helicase atp-binding domain; an α-helix

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.Pro515Arg Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro515= Likely benign ★ same residue
RECQL4 p.Pro515Leu 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
RECQL4 c.1704+2T>G 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-pro515ser (accessed [today's date]).

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