Is RECQL4 p.Ser246= (c.738C>T) pathogenic?

RECQL4 p.Ser246= (c.738C>T) is classified Benign in RECQL4 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 50.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ser246= (c.738C>T)?

RECQL4 p.Ser246= (c.738C>T) is associated with Baller-Gerold syndrome, rapadilino syndrome, Rothmund-Thomson syndrome type 2 (ClinVar).

RECQL4 p.Ser246=

Q: How common is RECQL4 p.Ser246= (c.738C>T) in the general population?

RECQL4 p.Ser246= (c.738C>T) is common (popmax 50.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.738C>T · rs4244613 · VCV94897

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 50.8%, sas) — too common for a highly-penetrant pathogenic allele

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 -1.2	GERP -2.2
Overall
CADD	0.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.8% South Asian · 46,184/90,970 alleles

Filtering AF 50.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 50.2%

Overall 43.1% 693,672/1,609,020 alleles · common exomes 637,528/1,456,878 · genomes 56,144/152,142 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	50.8%	2
Admixed American	50.6%	2
Finnishnot grpmax-eligible	48.3%	2
European (non-Finnish)	44.1%	2
Remaining individualsnot grpmax-eligible	41.8%	2
East Asian	40.3%	2
Ashkenazi Jewishnot grpmax-eligible	35.8%	3
Middle Eastern	29.6%	3
Amishnot grpmax-eligible	18.6%	5
African / African-American	15.2%	7

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.Ser246=
Coding: c.738C>T
MANE Select: NM_004260
dbSNP: rs4244613
Type: single nucleotide variant
Location: chr8:144516381 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 246: 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

Also linked: rapadilino syndrome Rothmund-Thomson syndrome type 2

Similar variants

RECQL4 p.Ser246Arg Uncertain significance ★ ⚠ same residue
RECQL4 p.Ser246Thr Uncertain significance ★ ⚠ same residue
RECQL4 p.Ser246Ile 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-ser246 (accessed [today's date]).

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