Is DBR1 p.His312Arg (c.935A>G) pathogenic?

DBR1 p.His312Arg (c.935A>G) is classified Uncertain significance in DBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-18). AlphaMissense: likely benign (0.2123); Absent from gnomAD v4.1.

How common is DBR1 p.His312Arg (c.935A>G) in the general population?

DBR1 p.His312Arg (c.935A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DBR1 p.His312Arg (c.935A>G)?

AlphaMissense predicts likely benign (score 0.2123) — an in-silico prediction, not a clinical call.

DBR1 p.His312Arg

c.935A>G · rs2472961645 · VCV2777799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2123 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2123	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -6.23	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 7.9	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DBR1
Protein: p.His312Arg
Coding: c.935A>G
MANE Select: NM_016216
dbSNP: rs2472961645
Type: single nucleotide variant
Location: chr3:138163355 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04
Residue 312: 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-his312arg (accessed [today's date]).

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