Is RECQL p.Asp413His (c.1237G>C) pathogenic?

RECQL p.Asp413His (c.1237G>C) is classified Uncertain significance in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.3668); Ultra-rare (popmax 0.0396%, sas).

How common is RECQL p.Asp413His (c.1237G>C) in the general population?

RECQL p.Asp413His (c.1237G>C) is ultra-rare (popmax 0.0396%, sas) (gnomAD).

What do computational predictors say about RECQL p.Asp413His (c.1237G>C)?

AlphaMissense predicts ambiguous (score 0.3668) — an in-silico prediction, not a clinical call.

RECQL p.Asp413His

c.1237G>C · rs556850507 · VCV1027189

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0396%, sas)

Computational evidence

Protein change
AlphaMissense	0.3668	ambiguous
REVEL	0.364	indeterminate
SaProt	LLR -8.41	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.095 · regional, not allelic
Overall
CADD	23.3	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 0.0396% South Asian · 36/91,004 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00236% 38/1,612,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0396%	2,528
Remaining individualsnot grpmax-eligible	0.0032%	31,226

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.Asp413His
Coding: c.1237G>C
MANE Select: NM_002907
dbSNP: rs556850507
Type: single nucleotide variant
Location: chr12:21474959 (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 413: the helicase c-terminal domain; a β-strand

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

Similar variants

RECQL p.Asp413Glu Uncertain significance ★★ same residue
RECQL p.Asp413= 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-asp413his (accessed [today's date]).

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