Is DBR1 p.Ile81Thr (c.242T>C) pathogenic?

DBR1 p.Ile81Thr (c.242T>C) is classified Uncertain significance in DBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). AlphaMissense: likely pathogenic (0.5669); Very rare (popmax 0.00267%, afr).

How common is DBR1 p.Ile81Thr (c.242T>C) in the general population?

DBR1 p.Ile81Thr (c.242T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DBR1 p.Ile81Thr (c.242T>C)?

AlphaMissense predicts likely pathogenic (score 0.5669) — an in-silico prediction, not a clinical call.

DBR1 p.Ile81Thr

c.242T>C · rs755768934 · VCV2126677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5669	likely pathogenic
REVEL	0.702	pathogenic-leaning
SaProt	LLR -11.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 12 kb · p 0.4 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,924 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.0013% 21/1,613,806 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,462
East Asian	0.00223%	44,884
Admixed American	0.00167%	59,996
European (non-Finnish)	0.00144%	69,403

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.Ile81Thr
Coding: c.242T>C
MANE Select: NM_016216
dbSNP: rs755768934
Type: single nucleotide variant
Location: chr3:138173582 (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-ile81thr (accessed [today's date]).

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