Is RECQL p.Asp541= (c.1623T>C) pathogenic?

RECQL p.Asp541= (c.1623T>C) is classified Likely benign in RECQL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). Ultra-rare (popmax 0.0134%, eas).

How common is RECQL p.Asp541= (c.1623T>C) in the general population?

RECQL p.Asp541= (c.1623T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

RECQL p.Asp541=

c.1623T>C · rs777754347 · VCV1081676

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 0.21	GERP -1.9, phastCons 0.95
Overall
CADD	5.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,870 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000558% 9/1,613,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,478
Remaining individualsnot grpmax-eligible	0.0032%	31,220
Admixed American	0.00167%	59,872

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.Asp541=
Coding: c.1623T>C
MANE Select: NM_002907
dbSNP: rs777754347
Type: single nucleotide variant
Location: chr12:21471472 (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 541: 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.Asp541His Uncertain significance ★★ ⚠ same residue
RECQL p.Asp541Glu Uncertain significance ★ ⚠ same residue
RECQL p.Asp541fs 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-asp541 (accessed [today's date]).

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