Is RECQL4 p.Ser280= (c.840C>T) pathogenic?

RECQL4 p.Ser280= (c.840C>T) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Ser280= (c.840C>T)?

RECQL4 p.Ser280= (c.840C>T) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ser280= (c.840C>T) in the general population?

RECQL4 p.Ser280= (c.840C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

RECQL4 p.Ser280=

c.840C>T · rs1407076588 · VCV743869

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.78	GERP -0.64, phastCons 0.019
Overall
CADD	2.457	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,068 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000496% 8/1,611,492 alleles · ultra-rare exomes 7/1,459,270 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,034
Remaining individualsnot grpmax-eligible	0.0016%	62,416
European (non-Finnish)	0.000424%	235,872

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.Ser280=
Coding: c.840C>T
MANE Select: NM_004260
dbSNP: rs1407076588
Type: single nucleotide variant
Location: chr8:144516279 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 280: the 'disordered' region

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.Ser280Asn Uncertain significance ★★ ⚠ same residue
RECQL4 p.Ser280Arg 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
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-ser280 (accessed [today's date]).

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