Is RECQL4 p.Arg418Pro (c.1253G>C) pathogenic?

RECQL4 p.Arg418Pro (c.1253G>C) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.0817); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Arg418Pro (c.1253G>C)?

RECQL4 p.Arg418Pro (c.1253G>C) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg418Pro (c.1253G>C) in the general population?

RECQL4 p.Arg418Pro (c.1253G>C) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about RECQL4 p.Arg418Pro (c.1253G>C)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

RECQL4 p.Arg418Pro

c.1253G>C · rs548957135 · VCV644335

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
SaProt	LLR -6.58	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 -0.18	GERP -2.3
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	3.338	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 0.0156% East Asian · 7/44,854 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000558% 9/1,612,210 alleles · ultra-rare exomes 6/1,459,916 · genomes 3/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,408
African / African-American	0.00133%	75,036
European (non-Finnish)	8.48e-05%	1,179,624

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.Arg418Pro
Coding: c.1253G>C
MANE Select: NM_004260
dbSNP: rs548957135
Type: single nucleotide variant
Location: chr8:144515769 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

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.Arg418Trp Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg418Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Arg418= Likely benign ★ same residue
RECQL4 p.Arg418fs Pathogenic ★ same residue
RECQL4 p.Arg418Gln 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-arg418pro (accessed [today's date]).

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