Is RECQL4 p.Ala239Pro (c.715G>C) pathogenic?

RECQL4 p.Ala239Pro (c.715G>C) is classified Uncertain significance in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely benign (0.0815); Very rare (popmax 0.00133%, afr); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ala239Pro (c.715G>C)?

RECQL4 p.Ala239Pro (c.715G>C) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ala239Pro (c.715G>C) in the general population?

RECQL4 p.Ala239Pro (c.715G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RECQL4 p.Ala239Pro (c.715G>C)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

RECQL4 p.Ala239Pro

c.715G>C · rs1286829220 · VCV2729050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.3
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	2.337	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,940 alleles

Overall 6.21e-05% 1/1,609,450 alleles · very rare exomes 0/1,457,212 · genomes 1/152,238 · joint denominator

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.Ala239Pro
Coding: c.715G>C
MANE Select: NM_004260
dbSNP: rs1286829220
Type: single nucleotide variant
Location: chr8:144516404 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 239: 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

Similar variants

RECQL4 p.Ala239Asp Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala239Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala239Thr Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala239Val Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Ala239= Likely benign ★ same residue
RECQL4 p.Ala239fs Pathogenic ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/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-ala239pro (accessed [today's date]).

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