Is AVPR2 p.His80Tyr (c.238C>T) pathogenic?

AVPR2 p.His80Tyr (c.238C>T) is classified Pathogenic in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.7548); Absent from gnomAD v4.1.

How common is AVPR2 p.His80Tyr (c.238C>T) in the general population?

AVPR2 p.His80Tyr (c.238C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVPR2 p.His80Tyr (c.238C>T)?

AlphaMissense predicts likely pathogenic (score 0.7548) — an in-silico prediction, not a clinical call.

AVPR2 p.His80Tyr

c.238C>T · rs2521152705 · VCV2152356

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7548 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7548	likely pathogenic ✓ concordant with ClinVar
REVEL	0.561	indeterminate
SaProt	LLR -12.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	25.3	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

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: AVPR2
Protein: p.His80Tyr
Coding: c.238C>T
MANE Select: NM_000054
dbSNP: rs2521152705
Type: single nucleotide variant
Location: chrX:153905744 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 80: an α-helix; a UniProt-annotated variant site (in ndi1)

Full AVPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
AVPR2 p.Arg113Trp Pathogenic ★★ same type
AVPR2 p.Arg137Cys Pathogenic ★★ same type
AVPR2 p.Arg137His Pathogenic ★★ same type
AVPR2 p.Arg181Cys Pathogenic ★★ ⚠ same type
AVPR2 p.Arg202Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
AVPR2 p.Arg337Ter Pathogenic ★★ same type
AVPR2 p.Asp85Asn Pathogenic ★★ 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/avpr2-p-his80tyr (accessed [today's date]).

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