Is RECQL4 p.Pro205= (c.615C>G) pathogenic?

RECQL4 p.Pro205= (c.615C>G) is classified Conflicting classifications of pathogenicity in RECQL4 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-03-01). Rare (popmax 0.291%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Pro205= (c.615C>G)?

RECQL4 p.Pro205= (c.615C>G) is associated with Inborn genetic diseases, Baller-Gerold syndrome, hereditary neoplastic syndrome (ClinVar).

How common is RECQL4 p.Pro205= (c.615C>G) in the general population?

RECQL4 p.Pro205= (c.615C>G) is rare (popmax 0.291%, nfe) (gnomAD).

RECQL4 p.Pro205=

c.615C>G · rs35639991 · VCV239780

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.291%, nfe)

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 -2	GERP -2.7
Overall
CADD	0.256	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.291% European (non-Finnish) · 3,433/1,179,568 alleles

Filtering AF 0.283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.228% 3,664/1,608,960 alleles · rare exomes 3,436/1,456,602 · genomes 228/152,358 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.291%	344
Remaining individualsnot grpmax-eligible	0.189%	529
Finnishnot grpmax-eligible	0.0737%	1,356
Admixed American	0.0517%	1,932
African / African-American	0.0466%	2,144
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,859

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.Pro205=
Coding: c.615C>G
MANE Select: NM_004260
dbSNP: rs35639991
Type: single nucleotide variant
Location: chr8:144516504 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 205: 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 hereditary neoplastic syndrome

Similar variants

RECQL4 p.Pro205Leu 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-pro205 (accessed [today's date]).

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