Is RECQL p.His260= (c.780C>T) pathogenic?

RECQL p.His260= (c.780C>T) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-22). Very rare (popmax 0.00334%, amr).

How common is RECQL p.His260= (c.780C>T) in the general population?

RECQL p.His260= (c.780C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

RECQL p.His260=

c.780C>T · rs767546518 · VCV1093926

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

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 -1.9	GERP -3.5
Overall
CADD	2.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,950 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00161% 26/1,613,808 alleles · very rare exomes 25/1,461,630 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,975
East Asian	0.00223%	44,886
European (non-Finnish)	0.00178%	56,186
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asian	0.0011%	91,046

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.His260=
Coding: c.780C>T
MANE Select: NM_002907
dbSNP: rs767546518
Type: single nucleotide variant
Location: chr12:21477890 (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 260: 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.His260Gln Uncertain significance ★★ ⚠ same residue
RECQL p.His260Pro Uncertain significance ★★ ⚠ same residue
RECQL p.His260Tyr 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-his260 (accessed [today's date]).

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