Is AGPS c.*4253C>A pathogenic?

AGPS c.4253C>A is classified Benign in AGPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-13). Common (popmax 94.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with rhizomelic chondrodysplasia punctata type 3.

What condition is associated with AGPS c.*4253C>A?

AGPS c.*4253C>A is associated with rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How is Rhizomelic chondrodysplasia punctata inherited?

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

AGPS c.*4253C>A

Q: How common is AGPS c.*4253C>A in the general population?

AGPS c.*4253C>A is common (popmax 94.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs10803912 · VCV332592

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 94.8%, eas) — too common for a highly-penetrant pathogenic allele

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 0.58	GERP -3.8
Non-coding constraint	Z 0.73	1 kb window · o/e 0.93 · regional · uncalibrated
Overall
CADD	0.405	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.8% East Asian · 4,908/5,176 alleles

Filtering AF 92.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 91.7%

Overall 84.2% 128,068/152,144 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	94.8%	1
Amishnot grpmax-eligible	93.8%	1
South Asian	89.2%	1
Finnishnot grpmax-eligible	87.1%	1
Admixed American	86.6%	1
European (non-Finnish)	84%	1
Remaining individualsnot grpmax-eligible	84%	1
Middle Eastern	82.7%	1
Ashkenazi Jewishnot grpmax-eligible	81.9%	1
African / African-American	80.9%	1

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
Coding: c.*4253C>A
MANE Select: NM_003659
dbSNP: rs10803912
Type: single nucleotide variant
Location: chr2:177542448 (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-c-star-4253c-a (accessed [today's date]).

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