Is AVP p.Leu135= (c.403C>T) pathogenic?

AVP p.Leu135= (c.403C>T) is classified Likely benign in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Very rare (popmax 0.00254%, nfe).

How common is AVP p.Leu135= (c.403C>T) in the general population?

AVP p.Leu135= (c.403C>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

AVP p.Leu135=

c.403C>T · rs1009997849 · VCV2905309

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

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 4.7	GERP 0.45, phastCons 1
Overall
CADD	12.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 26/1,023,810 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0015%

Overall 0.00217% 28/1,293,050 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00254%	39,377
Remaining individualsnot grpmax-eligible	0.00209%	47,842
African / African-American	0.00155%	64,452

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.Leu135=
Coding: c.403C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs1009997849
Type: single nucleotide variant
Location: chr20:3082722 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB

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

Similar variants

NLRP3 p.Arg135Gly Uncertain significance ★ ⚠ same residue
NLRP3 p.Arg135His Conflicting classifications of pathogenicity ★ ⚠ same residue
NLRP3 p.Arg135Pro Uncertain significance ★ ⚠ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same type
AVP p.Cys92Tyr Likely pathogenic ★★ same type
AVP p.Glu108Ter Pathogenic ★★ same type
AVP p.Gly54Arg Pathogenic ★★ same type
AVP p.Gly96Asp Pathogenic/Likely 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/avp-p-leu135 (accessed [today's date]).

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