Is DBR1 p.Ser451Leu (c.1352C>T) pathogenic?

DBR1 p.Ser451Leu (c.1352C>T) is classified Likely benign in DBR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.068); Rare (popmax 0.344%, nfe).

How common is DBR1 p.Ser451Leu (c.1352C>T) in the general population?

DBR1 p.Ser451Leu (c.1352C>T) is rare (popmax 0.344%, nfe) (gnomAD).

What do computational predictors say about DBR1 p.Ser451Leu (c.1352C>T)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

DBR1 p.Ser451Leu

c.1352C>T · rs114451412 · VCV2053955

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.344%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 490 bp · p 0.31 · regional, not allelic
Overall
CADD	22.2	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 0.344% European (non-Finnish) · 4,057/1,180,034 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.282% 4,557/1,614,126 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.344%	291
East Asian	0.254%	394
Remaining individualsnot grpmax-eligible	0.205%	488
Finnishnot grpmax-eligible	0.147%	681
Admixed American	0.0866%	1,154
South Asian	0.0791%	1,265
African / African-American	0.052%	1,924
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Ser451Leu
Coding: c.1352C>T
MANE Select: NM_016216
dbSNP: rs114451412
Type: single nucleotide variant
Location: chr3:138162172 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 451: 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 p.Ser451= Likely benign ★ same residue
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

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-ser451leu (accessed [today's date]).

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