Is AVPR1A p.Phe136= (c.408T>C) pathogenic?

AVPR1A p.Phe136= (c.408T>C) is classified Benign in AVPR1A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-22). Common (popmax 83.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with AVPR1A-related disorder.

What condition is associated with AVPR1A p.Phe136= (c.408T>C)?

AVPR1A p.Phe136= (c.408T>C) is associated with AVPR1A-related disorder (ClinVar).

AVPR1A p.Phe136=

Q: How common is AVPR1A p.Phe136= (c.408T>C) in the general population?

AVPR1A p.Phe136= (c.408T>C) is common (popmax 83.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.408T>C · rs1042615 · VCV3060712

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 83.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

AVPR1A-related disorder

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 1.5	GERP -2.5, phastCons 1
Overall
CADD	8.732	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 83.4% African / African-American · 62,547/75,034 alleles

Filtering AF 82.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 82.6%

Overall 58.8% 947,639/1,612,908 alleles · common exomes 848,579/1,460,734 · genomes 99,060/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	83.4%	1
Middle Eastern	69.6%	1
South Asian	68.9%	1
Ashkenazi Jewishnot grpmax-eligible	68.6%	1
Admixed American	61.5%	2
Remaining individualsnot grpmax-eligible	61.1%	2
Finnishnot grpmax-eligible	58.2%	2
European (non-Finnish)	56.2%	2
Amishnot grpmax-eligible	55.6%	2
East Asian	49.1%	2

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: AVPR1A
Protein: p.Phe136=
Coding: c.408T>C
MANE Select: NM_000706
dbSNP: rs1042615
Type: single nucleotide variant
Location: chr12:63150429 (GRCh38)
Gene constraint: LOEUF 1.264 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.11 · 5 PDB

Full AVPR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AVPR1A-related disorder

Similar variants

AVPR1A p.Ile243Phe Uncertain significance ★ ⚠ same condition
AVPR1A p.Phe308Leu Benign ★★ ⚠ same type
AVPR1A p.Ala227Glu Uncertain significance ★ ⚠ same type
AVPR1A p.Ala252Val Uncertain significance ★ ⚠ same type
AVPR1A p.Ala65Thr Uncertain significance ★ ⚠ same type
AVPR1A p.Arg118His Uncertain significance ★ ⚠ same type
AVPR1A p.Arg288Cys Uncertain significance ★ same type
AVPR1A p.Arg2His 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/avpr1a-p-phe136 (accessed [today's date]).

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