Is AGPS p.Arg62= (c.186A>G) pathogenic?

AGPS p.Arg62= (c.186A>G) is classified Benign in AGPS (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0612%, eas); Associated with rhizomelic chondrodysplasia punctata.

What condition is associated with AGPS p.Arg62= (c.186A>G)?

AGPS p.Arg62= (c.186A>G) is associated with rhizomelic chondrodysplasia punctata (ClinVar).

How common is AGPS p.Arg62= (c.186A>G) in the general population?

AGPS p.Arg62= (c.186A>G) is ultra-rare (popmax 0.0612%, eas) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

AGPS p.Arg62=

c.186A>G · rs990214554 · VCV713194

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0612%, eas)

Conditions

rhizomelic chondrodysplasia punctata

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 6.4	GERP 1.7, phastCons 1
Overall
CADD	15.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0612% East Asian · 25/40,872 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0362%

Overall 0.00168% 26/1,549,840 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0612%	1,635
Remaining individualsnot grpmax-eligible	0.00167%	60,056

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.Arg62=
Coding: c.186A>G
MANE Select: NM_003659
dbSNP: rs990214554
Type: single nucleotide variant
Location: chr2:177392975 (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 — 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.Thr309Ile Likely pathogenic ★★ same condition
AGPS c.261-5A>C Benign ★★ same condition
AGPS p.Ala69= Benign ★★ same condition
AGPS p.His362= Likely benign ★★ same condition
AGPS p.Pro415= Benign/Likely benign ★★ same condition
AGPS p.Pro49= Benign/Likely benign ★★ same condition
AGPS p.Ala5Val Uncertain significance ★ ⚠ same condition
AGPS p.Arg50Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg62 (accessed [today's date]).

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