Is AGPS p.Gly343= (c.1029T>C) pathogenic?

AGPS p.Gly343= (c.1029T>C) is classified Likely benign in AGPS (ClinVar, Single submitter, 3 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0359%, mid); Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Gly343= (c.1029T>C)?

AGPS p.Gly343= (c.1029T>C) is associated with rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How common is AGPS p.Gly343= (c.1029T>C) in the general population?

AGPS p.Gly343= (c.1029T>C) is ultra-rare (popmax 0.0359%, mid) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AGPS p.Gly343=

c.1029T>C · rs368667324 · VCV740034

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0359%, mid)

Conditions

rhizomelic chondrodysplasia punctata type 3

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 0.29	GERP 1, phastCons 0.99
Overall
CADD	8.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0359% Middle Eastern · 2/5,574 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00906% 146/1,611,866 alleles · ultra-rare exomes 133/1,459,740 · genomes 13/152,126 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0359%	2,787
Admixed American	0.0233%	4,285
Remaining individualsnot grpmax-eligible	0.0112%	8,912
European (non-Finnish)	0.0102%	9,823
African / African-American	0.004%	24,994

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: AGPS
Protein: p.Gly343=
Coding: c.1029T>C
MANE Select: NM_003659
dbSNP: rs368667324
Type: single nucleotide variant
Location: chr2:177468448 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 343: the fad-binding pcmh-type domain

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

Disease context

rhizomelic chondrodysplasia punctata type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rhizomelic chondrodysplasia punctata (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same condition
AGPS p.Thr309Ile Likely pathogenic ★★ same condition
AGPS c.1855+6C>A Uncertain significance ★★ same condition
AGPS c.*118A>G Uncertain significance ★★ same condition
AGPS p.Asp28Val Uncertain significance ★★ ⚠ same condition
AGPS p.Pro415Leu Uncertain significance ★★ ⚠ same condition
AGPS p.Thr72Ala Uncertain significance ★★ ⚠ same condition
AGPS c.1233+14T>A Benign/Likely benign ★★ 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/agps-p-gly343 (accessed [today's date]).

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