Is AGXT p.Lys229= (c.687G>A) pathogenic?

AGXT p.Lys229= (c.687G>A) is classified Likely benign in AGXT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). Very rare (popmax 0.000934%, nfe).

How common is AGXT p.Lys229= (c.687G>A) in the general population?

AGXT p.Lys229= (c.687G>A) is very rare (popmax 0.000934%, nfe) (gnomAD).

AGXT p.Lys229=

c.687G>A · rs770627873 · VCV2737930

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000934%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.5	GERP 0.84, phastCons 1
Overall
CADD	13.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000934% European (non-Finnish) · 11/1,177,908 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000807% 13/1,611,682 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,198
European (non-Finnish)grpmax	0.000934%	107,083

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AGXT
Protein: p.Lys229=
Coding: c.687G>A
MANE Select: NM_000030
dbSNP: rs770627873
Type: single nucleotide variant
Location: chr2:240875115 (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 229: an α-helix

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

Similar variants

AGXT p.Lys229del Likely pathogenic ★ same residue
AGXT p.Lys229dup Uncertain significance 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

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-lys229 (accessed [today's date]).

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