Is AGTR1 p.Ser342Pro (c.1024T>C) pathogenic?

AGTR1 p.Ser342Pro (c.1024T>C) is classified Uncertain significance in AGTR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1135); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGTR1 p.Ser342Pro (c.1024T>C)?

AGTR1 p.Ser342Pro (c.1024T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGTR1 p.Ser342Pro (c.1024T>C) in the general population?

AGTR1 p.Ser342Pro (c.1024T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGTR1 p.Ser342Pro (c.1024T>C)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

AGTR1 p.Ser342Pro

c.1024T>C · VCV4025397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1135	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 1,076 bp · p 0.0046 · regional, not allelic
Overall
CADD	21.7	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

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: AGTR1
Protein: p.Ser342Pro
Coding: c.1024T>C
MANE Select: NM_000685
Type: single nucleotide variant
Location: chr3:148742059 (GRCh38)
Gene constraint: LOEUF 1.113 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.55 · 14 PDB
Residue 342: the 'disordered' region

Full AGTR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGTR1 p.Asn46Lys Uncertain significance ★★ ⚠ same condition
AGTR1 p.Leu70Ile Uncertain significance ★★ ⚠ same condition
AGTR1 p.Phe356Val Uncertain significance ★★ ⚠ same condition
AGTR1 p.Thr260Ile Uncertain significance ★★ ⚠ same condition
AGTR1 p.Val52Gly Uncertain significance ★★ ⚠ same condition
AGTR1 p.Asn231Asp Uncertain significance ★ ⚠ same condition
AGTR1 p.Asp236Val Uncertain significance ★ same condition
AGTR1 p.Asp237Glu Uncertain significance ★ ⚠ 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/agtr1-p-ser342pro (accessed [today's date]).

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