Is RECQL4 p.Ser983= (c.2949C>T) pathogenic?

RECQL4 p.Ser983= (c.2949C>T) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). Ultra-rare (popmax 0.035%, amr); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ser983= (c.2949C>T)?

RECQL4 p.Ser983= (c.2949C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ser983= (c.2949C>T) in the general population?

RECQL4 p.Ser983= (c.2949C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

RECQL4 p.Ser983=

c.2949C>T · rs751727270 · VCV529088

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -3.9, phastCons 0.099
Overall
CADD	1.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/59,990 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00143% 23/1,612,402 alleles · ultra-rare exomes 13/1,460,156 · genomes 10/152,246 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
African / African-American	0.00133%	74,952
European (non-Finnish)	8.48e-05%	1,179,820

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.Ser983=
Coding: c.2949C>T
MANE Select: NM_004260
dbSNP: rs751727270
Type: single nucleotide variant
Location: chr8:144512498 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 983: a UniProt-annotated variant site (in rts2)

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.Ser983Asn 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
RECQL4 c.1705-1G>C 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-ser983 (accessed [today's date]).

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