Is RECQL p.Pro233Thr (c.697C>A) pathogenic?

RECQL p.Pro233Thr (c.697C>A) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-23). AlphaMissense: ambiguous (0.4917); Very rare (popmax 0.000767%, nfe).

How common is RECQL p.Pro233Thr (c.697C>A) in the general population?

RECQL p.Pro233Thr (c.697C>A) is very rare (popmax 0.000767%, nfe) (gnomAD).

What do computational predictors say about RECQL p.Pro233Thr (c.697C>A)?

AlphaMissense predicts ambiguous (score 0.4917) — an in-silico prediction, not a clinical call.

RECQL p.Pro233Thr

c.697C>A · rs371196239 · VCV1306263

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000767%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4917	ambiguous
REVEL	0.731	pathogenic-leaning
SaProt	LLR -12.60	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000767% European (non-Finnish) · 9/1,173,758 alleles

Filtering AF 0.000361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000261%

Overall 0.000563% 9/1,597,494 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.Pro233Thr
Coding: c.697C>A
MANE Select: NM_002907
dbSNP: rs371196239
Type: single nucleotide variant
Location: chr12:21483379 (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 233: the helicase atp-binding domain; an α-helix

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

Similar variants

RECQL p.Pro233Ser Uncertain significance ★★ ⚠ same residue
RECQL p.Pro233= Likely benign ★ 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
RECQL c.1667+5G>C 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-pro233thr (accessed [today's date]).

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