Is AGPS p.Gln290= (c.870G>A) pathogenic?

AGPS p.Gln290= (c.870G>A) is classified Uncertain significance in AGPS (ClinVar, Single submitter, 2 submitters; last evaluated 2020-02-14). Very rare (popmax 0.00952%, afr); Associated with rhizomelic chondrodysplasia punctata.

What condition is associated with AGPS p.Gln290= (c.870G>A)?

AGPS p.Gln290= (c.870G>A) is associated with rhizomelic chondrodysplasia punctata (ClinVar).

How common is AGPS p.Gln290= (c.870G>A) in the general population?

AGPS p.Gln290= (c.870G>A) is very rare (popmax 0.00952%, afr) (gnomAD).

How is Rhizomelic chondrodysplasia punctata inherited?

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

AGPS p.Gln290=

c.870G>A · rs534985206 · VCV991247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00952%, afr)

Conditions

rhizomelic chondrodysplasia punctata

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.7	GERP 1.5, phastCons 1
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00952% African / African-American · 7/73,496 alleles

Filtering AF 0.00445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00314%

Overall 0.000569% 9/1,581,334 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00952%	10,499
East Asian	0.00226%	44,338
Remaining individualsnot grpmax-eligible	0.00164%	61,044

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.Gln290=
Coding: c.870G>A
MANE Select: NM_003659
dbSNP: rs534985206
Type: single nucleotide variant
Location: chr2:177445626 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 290: 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 — 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-gln290 (accessed [today's date]).

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