Is RECQL p.Phe420Ser (c.1259T>C) pathogenic?

RECQL p.Phe420Ser (c.1259T>C) is classified Uncertain significance in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: likely pathogenic (0.8574); Very rare (popmax 8.48e-05%, nfe).

How common is RECQL p.Phe420Ser (c.1259T>C) in the general population?

RECQL p.Phe420Ser (c.1259T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about RECQL p.Phe420Ser (c.1259T>C)?

AlphaMissense predicts likely pathogenic (score 0.8574) — an in-silico prediction, not a clinical call.

RECQL p.Phe420Ser

c.1259T>C · rs1439925482 · VCV1762609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8574 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8574	likely pathogenic
REVEL	0.713	pathogenic-leaning
SaProt	LLR -13.12	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,184 alleles

Overall 0.000658% 1/152,042 alleles · very rare

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: RECQL
Protein: p.Phe420Ser
Coding: c.1259T>C
MANE Select: NM_002907
dbSNP: rs1439925482
Type: single nucleotide variant
Location: chr12:21474937 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.55 · 7 PDB
Residue 420: the helicase c-terminal domain; an α-helix

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

Similar variants

RECQL p.Phe420Leu Uncertain significance ★ ⚠ same residue
RECQL p.Phe420= Likely benign ★ same residue
RECQL p.Phe420fs Uncertain significance ★★ same residue
RECQL c.1098+1G>A Uncertain significance ★★ same type
RECQL c.1216+3A>G Uncertain significance ★★ same type
RECQL c.1217-3C>T Uncertain significance ★★ same type
RECQL c.1355+1G>A Uncertain significance ★★ same type
RECQL c.1356-12A>G Uncertain significance ★★ same type

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/recql-p-phe420ser (accessed [today's date]).

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