Is RECQL4 p.Arg76Ser (c.226C>A) pathogenic?

RECQL4 p.Arg76Ser (c.226C>A) is classified Uncertain significance in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-31). AlphaMissense: likely benign (0.0801); No allele count reported in gnomAD v4.1 (AN 1,605,160); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Arg76Ser (c.226C>A)?

RECQL4 p.Arg76Ser (c.226C>A) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Arg76Ser (c.226C>A) in the general population?

RECQL4 p.Arg76Ser (c.226C>A) is no allele count reported in gnomAD v4.1 (AN 1,605,160) (gnomAD).

What do computational predictors say about RECQL4 p.Arg76Ser (c.226C>A)?

AlphaMissense predicts likely benign (score 0.0801) — an in-silico prediction, not a clinical call.

RECQL4 p.Arg76Ser

c.226C>A · rs1815254850 · VCV2149877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0801 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,160)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0801	likely benign
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.32	GERP -1.6
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	0.408	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

No allele count reported in gnomAD v4.1 (AN 1,605,160). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RECQL4
Protein: p.Arg76Ser
Coding: c.226C>A
MANE Select: NM_004260
dbSNP: rs1815254850
Type: single nucleotide variant
Location: chr8:144517178 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 76: 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.Arg76Cys Uncertain significance ★★ ⚠ same residue
RECQL4 p.Arg76His Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Arg76Leu 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-arg76ser (accessed [today's date]).

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