Is DBR1 p.Asp541= (c.1623C>T) pathogenic?

DBR1 p.Asp541= (c.1623C>T) is classified Benign/Likely benign in DBR1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 68.2%, nfe) — too common for a highly-penetrant pathogenic allele.

DBR1 p.Asp541=

Q: How common is DBR1 p.Asp541= (c.1623C>T) in the general population?

DBR1 p.Asp541= (c.1623C>T) is common (popmax 68.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1623C>T · rs2622736 · VCV2115209

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 68.2%, nfe) — too common for a highly-penetrant pathogenic allele

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 -0.53	GERP -2, phastCons 0.017
Overall
CADD	3.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 68.2% European (non-Finnish) · 792,632/1,161,770 alleles

Filtering AF 68.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 68%

Overall 66% 1,050,457/1,591,570 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	68.2%	1
Ashkenazi Jewishnot grpmax-eligible	67.9%	1
Finnishnot grpmax-eligible	65.8%	2
Remaining individualsnot grpmax-eligible	65%	2
Middle Eastern	64.3%	2
Admixed American	63.6%	2
South Asian	59.2%	2
East Asian	55.2%	2
African / African-American	48.5%	2
Amishnot grpmax-eligible	47.9%	2

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: DBR1
Protein: p.Asp541=
Coding: c.1623C>T
MANE Select: NM_016216
dbSNP: rs2622736
Type: single nucleotide variant
Location: chr3:138161901 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 541: the 'disordered' region; a UniProt-annotated variant site (in iiae11; loss of protein expression)

Full DBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DBR1 c.489+5G>A Uncertain significance ★★ same type
DBR1 p.Ala233Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala443Thr Uncertain significance ★★ ⚠ same type
DBR1 p.Ala458Asp Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Gln Uncertain significance ★★ ⚠ same type
DBR1 p.Arg197Ter Uncertain significance ★★ same type
DBR1 p.Arg527Ser Uncertain significance ★★ ⚠ same type
DBR1 p.Asn405His 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/dbr1-p-asp541 (accessed [today's date]).

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