Is DBR1 p.Tyr65Cys (c.194A>G) pathogenic?

DBR1 p.Tyr65Cys (c.194A>G) is classified Uncertain significance in DBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely benign (0.2991); Very rare (popmax 0.00188%, amr).

How common is DBR1 p.Tyr65Cys (c.194A>G) in the general population?

DBR1 p.Tyr65Cys (c.194A>G) is very rare (popmax 0.00188%, amr) (gnomAD).

What do computational predictors say about DBR1 p.Tyr65Cys (c.194A>G)?

AlphaMissense predicts likely benign (score 0.2991) — an in-silico prediction, not a clinical call.

DBR1 p.Tyr65Cys

c.194A>G · rs769868644 · VCV2070661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00188%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2991	likely benign
REVEL	0.427	indeterminate
SaProt	LLR -11.05	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	31.0	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 0.00188% Admixed American · 1/53,282 alleles

Filtering AF 0.000336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000728% 9/1,236,794 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00188%	53,282
European (non-Finnish)	0.00078%	128,153

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.Tyr65Cys
Coding: c.194A>G
MANE Select: NM_016216
dbSNP: rs769868644
Type: single nucleotide variant
Location: chr3:138174602 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04

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-tyr65cys (accessed [today's date]).

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