Is GPC6 p.Asp504= (c.1512C>T) pathogenic?

GPC6 p.Asp504= (c.1512C>T) is classified Conflicting classifications of pathogenicity in GPC6 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-06-28). Ultra-rare (popmax 0.0267%, eas); Associated with autosomal recessive omodysplasia.

What condition is associated with GPC6 p.Asp504= (c.1512C>T)?

GPC6 p.Asp504= (c.1512C>T) is associated with autosomal recessive omodysplasia (ClinVar).

How common is GPC6 p.Asp504= (c.1512C>T) in the general population?

GPC6 p.Asp504= (c.1512C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

GPC6 p.Asp504=

c.1512C>T · rs776151903 · VCV882731

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Conditions

autosomal recessive omodysplasia

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 -8.8	GERP -4.5
Overall
CADD	1.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,872 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00161% 26/1,613,628 alleles · ultra-rare exomes 21/1,461,316 · genomes 5/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,739
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0022%	45,535
Admixed American	0.00167%	60,028
European (non-Finnish)	0.000763%	131,058

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: GPC6
Protein: p.Asp504=
Coding: c.1512C>T
MANE Select: NM_005708
dbSNP: rs776151903
Type: single nucleotide variant
Location: chr13:94403061 (GRCh38)
Gene constraint: LOEUF 0.384 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.67

Full GPC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive omodysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GPC6 p.Asp504Tyr Uncertain significance ★ ⚠ same residue
GPC6 p.Arg171Trp Pathogenic/Likely pathogenic ★★ same condition
GPC6 p.Ala377Thr Uncertain significance ★★ ⚠ same condition
GPC6 p.Arg363His Uncertain significance ★★ same condition
GPC6 p.Arg524Trp Uncertain significance ★★ ⚠ same condition
GPC6 p.Arg534His Uncertain significance ★★ ⚠ same condition
GPC6 p.Ile388Val Uncertain significance ★★ ⚠ same condition
GPC6 p.Ile406Val 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/gpc6-p-asp504 (accessed [today's date]).

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