Is AGXT p.Phe68Ser (c.203T>C) pathogenic?

AGXT p.Phe68Ser (c.203T>C) is classified Uncertain significance in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-01). AlphaMissense: likely pathogenic (0.8607); Absent from gnomAD v4.1.

How common is AGXT p.Phe68Ser (c.203T>C) in the general population?

AGXT p.Phe68Ser (c.203T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGXT p.Phe68Ser (c.203T>C)?

AlphaMissense predicts likely pathogenic (score 0.8607) — an in-silico prediction, not a clinical call.

AGXT p.Phe68Ser

c.203T>C · rs2106427539 · VCV1335452

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8607	likely pathogenic · top 10% in AGXT
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,952 bp · p 0.92 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: AGXT
Protein: p.Phe68Ser
Coding: c.203T>C
MANE Select: NM_000030
dbSNP: rs2106427539
Type: single nucleotide variant
Location: chr2:240869207 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.30 · 17 PDB
Residue 68: an α-helix

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

Similar variants

AGXT p.Phe68= Likely benign ★ same residue
AGXT c.358+1G>A Pathogenic ★★ same type
AGXT c.359-2A>G Likely pathogenic ★★ same type
AGXT c.423+1G>A Pathogenic/Likely pathogenic ★★ same type
AGXT c.524+2T>A Likely pathogenic ★★ same type
AGXT c.525-1G>A Pathogenic ★★ same type
AGXT c.525-2A>T Pathogenic/Likely pathogenic ★★ same type
AGXT c.595+1G>T 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/agxt-p-phe68ser (accessed [today's date]).

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