Is RECQL p.His340= (c.1020T>C) pathogenic?

RECQL p.His340= (c.1020T>C) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-18). Ultra-rare (popmax 0.0694%, afr).

How common is RECQL p.His340= (c.1020T>C) in the general population?

RECQL p.His340= (c.1020T>C) is ultra-rare (popmax 0.0694%, afr) (gnomAD).

RECQL p.His340=

c.1020T>C · rs141567619 · VCV515568

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0694%, afr)

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 -0.14	GERP -1.4
Overall
CADD	4.312	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0694% African / African-American · 52/74,908 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.049%

Overall 0.00341% 55/1,613,300 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0694%	1,441
Remaining individualsnot grpmax-eligible	0.0048%	20,816

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.His340=
Coding: c.1020T>C
MANE Select: NM_002907
dbSNP: rs141567619
Type: single nucleotide variant
Location: chr12:21475754 (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 340: the helicase c-terminal domain

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

Similar variants

RECQL p.His340Tyr Uncertain significance ★ ⚠ same residue
RECQL p.His340fs 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
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-his340 (accessed [today's date]).

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