Is RECQL p.Pro535= (c.1605C>A) pathogenic?

RECQL p.Pro535= (c.1605C>A) is classified Likely benign in RECQL (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-11). Very rare (popmax 0.0022%, sas).

How common is RECQL p.Pro535= (c.1605C>A) in the general population?

RECQL p.Pro535= (c.1605C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

RECQL p.Pro535=

c.1605C>A · rs746130237 · VCV1776251

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -1.4	GERP 1.2
Overall
CADD	5.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,024 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000248% 4/1,613,180 alleles · very rare exomes 4/1,461,006 · genomes 0/152,174 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,512
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	8.48e-05%	1,179,426

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.Pro535=
Coding: c.1605C>A
MANE Select: NM_002907
dbSNP: rs746130237
Type: single nucleotide variant
Location: chr12:21471490 (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 535: the 'winged-helix domain' region; an α-helix

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

Similar variants

RECQL p.Pro535Leu Uncertain significance ★★ same residue
RECQL p.Pro535Arg Uncertain significance ★ ⚠ same residue
RECQL p.Pro535His Uncertain significance ★ ⚠ same residue
RECQL p.Pro535Ser Uncertain significance ★ ⚠ same residue
RECQL p.Pro535Thr Uncertain significance ★ ⚠ same residue
RECQL p.Pro535fs Uncertain significance ★ same residue
RECQL c.1098+1G>A Uncertain significance ★★ same type
RECQL c.1216+3A>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-pro535 (accessed [today's date]).

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