Is AGPS p.Pro49= (c.147C>T) pathogenic?

AGPS p.Pro49= (c.147C>T) is classified Benign/Likely benign in AGPS (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.55%, nfe); Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS p.Pro49= (c.147C>T)?

AGPS p.Pro49= (c.147C>T) is associated with rhizomelic chondrodysplasia punctata type 3, rhizomelic chondrodysplasia punctata (ClinVar).

How common is AGPS p.Pro49= (c.147C>T) in the general population?

AGPS p.Pro49= (c.147C>T) is low-frequency (popmax 1.55%, nfe) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

AGPS p.Pro49=

c.147C>T · rs34442536 · VCV157711

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.55%, nfe)

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 -0.3	GERP -2.3, phastCons 0.14
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.55% European (non-Finnish) · 17,739/1,146,746 alleles

Filtering AF 1.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.52%

Overall 1.32% 20,440/1,550,112 alleles · low-frequency exomes 18,932/1,397,858 · genomes 1,508/152,254 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.82%	35
European (non-Finnish)grpmax	1.55%	65
Remaining individualsnot grpmax-eligible	0.907%	110
Admixed American	0.351%	285
African / African-American	0.215%	466
South Asian	0.177%	564
Middle Eastern	0.167%	599
East Asian	0.0122%	8,173
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,626

Finnish 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: AGPS
Protein: p.Pro49=
Coding: c.147C>T
MANE Select: NM_003659
dbSNP: rs34442536
Type: single nucleotide variant
Location: chr2:177392936 (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

Also linked: rhizomelic chondrodysplasia punctata

For Rhizomelic chondrodysplasia punctata (Orphanet):

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

Similar variants

AGPS p.Pro49Leu Uncertain significance ★ ⚠ same residue
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

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-pro49 (accessed [today's date]).

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