Is DBH p.Asp91Asn (c.271G>A) pathogenic?

DBH p.Asp91Asn (c.271G>A) is classified Uncertain significance in DBH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-12). AlphaMissense: likely benign (0.1137); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with DBH p.Asp91Asn (c.271G>A)?

DBH p.Asp91Asn (c.271G>A) is associated with Inborn genetic diseases, orthostatic hypotension 1 (ClinVar).

How common is DBH p.Asp91Asn (c.271G>A) in the general population?

DBH p.Asp91Asn (c.271G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about DBH p.Asp91Asn (c.271G>A)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

DBH p.Asp91Asn

c.271G>A · rs147944557 · VCV1424294

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.569	indeterminate
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.96 · regional, not allelic
Overall
CADD	23.3	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 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00335% 54/1,612,482 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
East Asian	0.00446%	22,445
European (non-Finnish)	0.00373%	26,818
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00267%	37,460
South Asian	0.0011%	91,070

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.Asp91Asn
Coding: c.271G>A
MANE Select: NM_000787
dbSNP: rs147944557
Type: single nucleotide variant
Location: chr9:133636642 (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 91: a β-strand; the domon domain

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

Also linked: orthostatic hypotension 1

Similar variants

DBH c.339+2T>C Pathogenic ★★ same condition
DBH c.1024+6C>T Uncertain significance ★★ same condition
DBH c.486+15C>T Uncertain significance ★★ same condition
DBH c.*393C>T Uncertain significance ★★ same condition
DBH p.Ala113Ser Uncertain significance ★★ ⚠ same condition
DBH p.Ala259Val Uncertain significance ★★ ⚠ same condition
DBH p.Ala383Val Uncertain significance ★★ ⚠ same condition
DBH p.Ala506Thr 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-asp91asn (accessed [today's date]).

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