Is AGPS p.Ala403= (c.1209C>T) pathogenic?

AGPS p.Ala403= (c.1209C>T) is classified Likely benign in AGPS (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-05). Ultra-rare (popmax 0.0168%, mid); Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Ala403= (c.1209C>T)?

AGPS p.Ala403= (c.1209C>T) is associated with rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How common is AGPS p.Ala403= (c.1209C>T) in the general population?

AGPS p.Ala403= (c.1209C>T) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

AGPS p.Ala403=

c.1209C>T · rs761638262 · VCV755357

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, 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 2.1	GERP 1.1, phastCons 1
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% Middle Eastern · 1/5,948 alleles

Filtering AF 0.00532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00526% 84/1,597,476 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,948
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,707
European (non-Finnish)	0.00649%	15,397
African / African-American	0.00269%	37,173
East Asian	0.00227%	44,008
Remaining individualsnot grpmax-eligible	0.00163%	61,538

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.Ala403=
Coding: c.1209C>T
MANE Select: NM_003659
dbSNP: rs761638262
Type: single nucleotide variant
Location: chr2:177482162 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27

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-ala403 (accessed [today's date]).

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