Is RECQL p.Ala217= (c.651T>C) pathogenic?

RECQL p.Ala217= (c.651T>C) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-05). Very rare (popmax 8.49e-05%, nfe); Associated with RECON progeroid syndrome.

What condition is associated with RECQL p.Ala217= (c.651T>C)?

RECQL p.Ala217= (c.651T>C) is associated with RECON progeroid syndrome (ClinVar).

How common is RECQL p.Ala217= (c.651T>C) in the general population?

RECQL p.Ala217= (c.651T>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

RECQL p.Ala217=

c.651T>C · rs776430701 · VCV2181206

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

RECON progeroid syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -3.1, phastCons 0.009
Overall
CADD	4.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,874 alleles

Overall 0.000657% 1/152,224 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.Ala217=
Coding: c.651T>C
MANE Select: NM_002907
dbSNP: rs776430701
Type: single nucleotide variant
Location: chr12:21483425 (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 217: the helicase atp-binding domain; a β-strand

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

Disease context

RECON progeroid syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL p.Ala217Ser Uncertain significance ★ ⚠ same residue
RECQL p.Ala217Thr Uncertain significance ★ same residue
RECQL p.Ala217Val Uncertain significance ★ ⚠ same residue
RECQL c.394+1G>A Uncertain significance ★★ same condition
RECQL c.867+3A>T Uncertain significance ★★ same condition
RECQL p.Ala459Ser Uncertain significance ★★ ⚠ same condition
RECQL p.Asp264Glu Uncertain significance ★★ ⚠ same condition
RECQL p.Asp72Gly Uncertain significance ★★ ⚠ 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/recql-p-ala217 (accessed [today's date]).

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