Is RECQL4 p.Ser64= (c.192G>C) pathogenic?

RECQL4 p.Ser64= (c.192G>C) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-11). Very rare (popmax 0.00402%, afr); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Ser64= (c.192G>C)?

RECQL4 p.Ser64= (c.192G>C) is associated with Inborn genetic diseases, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ser64= (c.192G>C) in the general population?

RECQL4 p.Ser64= (c.192G>C) is very rare (popmax 0.00402%, afr) (gnomAD).

RECQL4 p.Ser64=

c.192G>C · rs559507124 · VCV414242

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Conditions

Inborn genetic diseases

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 0.4	GERP -3.3, phastCons 0.72
Overall
CADD	4.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00402% African / African-American · 3/74,634 alleles

Filtering AF 0.00131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00109%

Overall 0.00177% 28/1,584,598 alleles · very rare exomes 22/1,432,302 · genomes 6/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,878
East Asian	0.00227%	43,998
European (non-Finnish)	0.00196%	50,894
Remaining individualsnot grpmax-eligible	0.00163%	61,406

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.Ser64=
Coding: c.192G>C
MANE Select: NM_004260
dbSNP: rs559507124
Type: single nucleotide variant
Location: chr8:144517435 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 64: 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.Ser64Ter Pathogenic ★ same residue
RECQL4 p.Ser64Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Ser64Trp 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-ser64 (accessed [today's date]).

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