Is AVP p.Ser17Phe (c.50C>T) pathogenic?

AVP p.Ser17Phe (c.50C>T) is classified Pathogenic in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: ambiguous (0.4537); Very rare (popmax 8.47e-05%, nfe); Associated with AVP-related disorder.

What condition is associated with AVP p.Ser17Phe (c.50C>T)?

AVP p.Ser17Phe (c.50C>T) is associated with AVP-related disorder (ClinVar).

How common is AVP p.Ser17Phe (c.50C>T) in the general population?

AVP p.Ser17Phe (c.50C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AVP p.Ser17Phe (c.50C>T)?

AlphaMissense predicts ambiguous (score 0.4537) — an in-silico prediction, not a clinical call.

AVP p.Ser17Phe

c.50C>T · VCV4944210

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4537 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

AVP-related disorder

Computational evidence

Protein change
AlphaMissense	0.4537	ambiguous
REVEL	0.698	pathogenic-leaning
SaProt	LLR -13.13	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 1,692 bp · p 5.5e-05 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.2e-05% 1/1,613,898 alleles · very rare exomes 1/1,461,516 · genomes 0/152,382 · joint denominator

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: AVP
Protein: p.Ser17Phe
Coding: c.50C>T
MANE Select: NM_000490
Type: single nucleotide variant
Location: chr20:3084625 (GRCh38)
Gene constraint: LOEUF 1.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.83 · 5 PDB
Residue 17: a UniProt-annotated variant site (in ndi)

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

Disease context

AVP-related disorder

Similar variants

AVP p.Ser17Pro Uncertain significance ★ ⚠ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same condition
AVP p.Cys92Tyr Likely pathogenic ★★ same condition
AVP p.Glu108Ter Pathogenic ★★ same condition
AVP p.Ser87Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVP c.121-2A>G Likely pathogenic ★ same condition
AVP p.Ala19Val Pathogenic ★ same condition
AVP p.Ala72Glu Likely pathogenic ★ same condition

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/avp-p-ser17phe (accessed [today's date]).

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