Is AVPR1B p.Arg348Trp (c.1042C>T) pathogenic?

AVPR1B p.Arg348Trp (c.1042C>T) is classified Uncertain significance in AVPR1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0741); Very rare (popmax 0.00891%, eas).

How common is AVPR1B p.Arg348Trp (c.1042C>T) in the general population?

AVPR1B p.Arg348Trp (c.1042C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about AVPR1B p.Arg348Trp (c.1042C>T)?

AlphaMissense predicts likely benign (score 0.0741) — an in-silico prediction, not a clinical call.

AVPR1B p.Arg348Trp

c.1042C>T · rs781960604 · VCV2484555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0741 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0741	likely benign
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.2
Regional constraint	o/e 1.07	unconstrained · MANE · 6,698 bp · p 0.11 · regional, not allelic
Overall
CADD	16.94	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 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00161% 26/1,613,636 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
African / African-American	0.004%	24,979
Remaining individualsnot grpmax-eligible	0.0032%	31,226
Admixed American	0.00167%	59,960
European (non-Finnish)	0.00127%	78,658
South Asian	0.0011%	91,044

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.Arg348Trp
Coding: c.1042C>T
MANE Select: NM_000707
dbSNP: rs781960604
Type: single nucleotide variant
Location: chr1:206110422 (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.Arg348Gln 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-arg348trp (accessed [today's date]).

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