Is AGT p.Ser68Cys (c.203C>G) pathogenic?

AGT p.Ser68Cys (c.203C>G) is classified Uncertain significance in AGT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-07). AlphaMissense: likely benign (0.169); Absent from gnomAD v4.1.

How common is AGT p.Ser68Cys (c.203C>G) in the general population?

AGT p.Ser68Cys (c.203C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGT p.Ser68Cys (c.203C>G)?

AlphaMissense predicts likely benign (score 0.169) — an in-silico prediction, not a clinical call.

AGT p.Ser68Cys

c.203C>G · rs753775475 · VCV2135150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.169 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.169	likely benign
REVEL	0.22	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.1, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 7,679 bp · p 0.88 · regional, not allelic
Overall
CADD	17.94	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S77C vs ClinVar S68C) — verify the residue.

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: AGT
Protein: p.Ser68Cys
Coding: c.203C>G
MANE Select: NM_001384479
dbSNP: rs753775475
Type: single nucleotide variant
Location: chr1:230710621 (GRCh38)
Gene constraint: LOEUF 1.202 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.74 · 22 PDB
Residue 68: a disulfide bond; an α-helix

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

Similar variants

AGT c.1060C>T Pathogenic/Likely pathogenic ★★ same type
AGT c.829+1G>T Pathogenic/Likely pathogenic ★★ same type
AGT c.1195G>A Uncertain significance ★★ ⚠ same type
AGT c.856G>T Uncertain significance ★★ ⚠ same type
AGT c.862C>T Uncertain significance ★★ ⚠ same type
AGT c.-17G>C Uncertain significance ★★ ⚠ same type
AGT p.Arg165Gln Uncertain significance ★★ same type
AGT p.Arg366Leu 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/agt-p-ser68cys (accessed [today's date]).

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