Is RECQL4 p.Pro441Ser (c.1321C>T) pathogenic?

RECQL4 p.Pro441Ser (c.1321C>T) is classified Benign/Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.0767); Rare (popmax 0.457%, eas); Associated with ovarian cancer.

What condition is associated with RECQL4 p.Pro441Ser (c.1321C>T)?

RECQL4 p.Pro441Ser (c.1321C>T) is associated with ovarian cancer, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro441Ser (c.1321C>T) in the general population?

RECQL4 p.Pro441Ser (c.1321C>T) is rare (popmax 0.457%, eas) (gnomAD).

What do computational predictors say about RECQL4 p.Pro441Ser (c.1321C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro441Ser

c.1321C>T · rs557142414 · VCV406952

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.457%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.23	GERP 0.86
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	2.31	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 0.457% East Asian · 205/44,884 alleles

Filtering AF 0.406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.386%

Overall 0.0133% 214/1,612,772 alleles · rare exomes 203/1,460,440 · genomes 11/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.457%	219
African / African-American	0.00666%	15,011
Remaining individualsnot grpmax-eligible	0.0032%	31,237
South Asian	0.0022%	45,542

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.Pro441Ser
Coding: c.1321C>T
MANE Select: NM_004260
dbSNP: rs557142414
Type: single nucleotide variant
Location: chr8:144515395 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 441: a UniProt-annotated variant site (in)

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Pro441Ala Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro441Leu 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

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-pro441ser (accessed [today's date]).

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