Is RECQL4 p.Pro338Ser (c.1012C>T) pathogenic?

RECQL4 p.Pro338Ser (c.1012C>T) is classified Uncertain significance in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely benign (0.0731); Very rare (popmax 0.00668%, eas); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro338Ser (c.1012C>T)?

RECQL4 p.Pro338Ser (c.1012C>T) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro338Ser (c.1012C>T) in the general population?

RECQL4 p.Pro338Ser (c.1012C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about RECQL4 p.Pro338Ser (c.1012C>T)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro338Ser

c.1012C>T · rs754299237 · VCV644143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
SaProt	LLR -6.17	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 -1.2	GERP 0.51
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	1.05	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 0.00668% East Asian · 3/44,890 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,612,896 alleles · very rare exomes 25/1,460,548 · genomes 0/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
European (non-Finnish)	0.00186%	53,631

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.Pro338Ser
Coding: c.1012C>T
MANE Select: NM_004260
dbSNP: rs754299237
Type: single nucleotide variant
Location: chr8:144516107 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

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.Pro338Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro338Thr Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro338= Likely benign ★★ same residue
RECQL4 p.Pro338His Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro338Ala 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

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-pro338ser (accessed [today's date]).

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