Is RECQL4 p.Ile703Val (c.2107A>G) pathogenic?

RECQL4 p.Ile703Val (c.2107A>G) is classified Conflicting classifications of pathogenicity in RECQL4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-15). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00875%, nfe); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Ile703Val (c.2107A>G)?

RECQL4 p.Ile703Val (c.2107A>G) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Ile703Val (c.2107A>G) in the general population?

RECQL4 p.Ile703Val (c.2107A>G) is very rare (popmax 0.00875%, nfe) (gnomAD).

What do computational predictors say about RECQL4 p.Ile703Val (c.2107A>G)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

RECQL4 p.Ile703Val

c.2107A>G · rs770227800 · VCV576878

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00875%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
SaProt	LLR -5.87	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 -6.7	GERP -3.5
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	1.159	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00875% European (non-Finnish) · 101/1,153,880 alleles

Filtering AF 0.00732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00683%

Overall 0.00679% 106/1,562,198 alleles · very rare exomes 100/1,410,316 · genomes 6/151,882 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00875%	11,425
African / African-American	0.00408%	24,507
Admixed American	0.00384%	26,027

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.Ile703Val
Coding: c.2107A>G
MANE Select: NM_004260
dbSNP: rs770227800
Type: single nucleotide variant
Location: chr8:144513664 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 703: the helicase c-terminal domain; a β-strand

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.Ile703= Likely benign ★★ same residue
RECQL4 p.Ile703Asn Uncertain significance ★ ⚠ same residue
RECQL4 p.Ile703Met 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-ile703val (accessed [today's date]).

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