Is AVPR1B p.Thr378= (c.1134G>T) pathogenic?

AVPR1B p.Thr378= (c.1134G>T) is classified Likely benign in AVPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-20). Ultra-rare (popmax 0.0117%, amr).

How common is AVPR1B p.Thr378= (c.1134G>T) in the general population?

AVPR1B p.Thr378= (c.1134G>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

AVPR1B p.Thr378=

c.1134G>T · rs782145142 · VCV721385

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.9
Overall
CADD	0.467	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,874 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00304% 49/1,612,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,553
European (non-Finnish)	0.00356%	28,087

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: AVPR1B
Protein: p.Thr378=
Coding: c.1134G>T
MANE Select: NM_000707
dbSNP: rs782145142
Type: single nucleotide variant
Location: chr1:206110330 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.18

Full AVPR1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AVPR1B p.Thr378Met Uncertain significance ★ ⚠ same residue
AVPR1B p.Leu113Val Uncertain significance ★★ ⚠ same type
AVPR1B p.Thr129= Likely benign ★★ same type
AVPR1B p.Trp187Arg Likely benign ★★ same type
AVPR1B p.Ala319Thr Uncertain significance ★ ⚠ same type
AVPR1B p.Ala34Thr Uncertain significance ★ ⚠ same type
AVPR1B p.Arg132Cys Uncertain significance ★ ⚠ same type
AVPR1B p.Arg141His 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/avpr1b-p-thr378 (accessed [today's date]).

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