Is DBH p.Ser611Gly (c.1831A>G) pathogenic?

DBH p.Ser611Gly (c.1831A>G) is classified Uncertain significance in DBH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely benign (0.0665); Ultra-rare (popmax 0.0275%, sas); Associated with Inborn genetic diseases.

What condition is associated with DBH p.Ser611Gly (c.1831A>G)?

DBH p.Ser611Gly (c.1831A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DBH p.Ser611Gly (c.1831A>G) in the general population?

DBH p.Ser611Gly (c.1831A>G) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

What do computational predictors say about DBH p.Ser611Gly (c.1831A>G)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

DBH p.Ser611Gly

c.1831A>G · rs568326839 · VCV2480061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.25	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 1.3	GERP 0.2, phastCons 0.097
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	13.02	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% South Asian · 25/90,926 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00186% 30/1,612,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,637
Remaining individualsnot grpmax-eligible	0.00801%	12,490

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: DBH
Protein: p.Ser611Gly
Coding: c.1831A>G
MANE Select: NM_000787
dbSNP: rs568326839
Type: single nucleotide variant
Location: chr9:133658424 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 1 PDB
Residue 611: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DBH p.Ser611Thr Uncertain significance ★ ⚠ same residue
DBH p.Ser611Asn Likely benign ★ same residue
DBH p.Ala113Ser Uncertain significance ★★ ⚠ same condition
DBH p.Ala383Val Uncertain significance ★★ ⚠ same condition
DBH p.Arg43His Uncertain significance ★★ ⚠ same condition
DBH p.Arg473Gln Uncertain significance ★★ ⚠ same condition
DBH p.Arg549Leu Uncertain significance ★★ ⚠ same condition
DBH p.Arg572His Uncertain significance ★★ ⚠ same condition

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/dbh-p-ser611gly (accessed [today's date]).

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