Is GPC6 p.Ser495= (c.1485A>T) pathogenic?

GPC6 p.Ser495= (c.1485A>T) is classified Conflicting classifications of pathogenicity in GPC6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-15). Rare (popmax 0.253%, afr); Associated with autosomal recessive omodysplasia.

What condition is associated with GPC6 p.Ser495= (c.1485A>T)?

GPC6 p.Ser495= (c.1485A>T) is associated with autosomal recessive omodysplasia (ClinVar).

How common is GPC6 p.Ser495= (c.1485A>T) in the general population?

GPC6 p.Ser495= (c.1485A>T) is rare (popmax 0.253%, afr) (gnomAD).

GPC6 p.Ser495=

c.1485A>T · rs140343089 · VCV312551

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.253%, afr)

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 -5.3	GERP -4.5
Overall
CADD	0.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.253% African / African-American · 190/75,008 alleles

Filtering AF 0.224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0376% 607/1,612,400 alleles · rare exomes 462/1,460,078 · genomes 145/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.253%	395
Admixed American	0.133%	750
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Remaining individualsnot grpmax-eligible	0.064%	1,561
European (non-Finnish)	0.0225%	4,447
South Asian	0.00439%	22,763
Finnishnot grpmax-eligible	0.00156%	64,048

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.Ser495=
Coding: c.1485A>T
MANE Select: NM_005708
dbSNP: rs140343089
Type: single nucleotide variant
Location: chr13:94403034 (GRCh38)
Gene constraint: LOEUF 0.384 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.67
Residue 495: the 'disordered' region

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.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
GPC6 p.Leu17Ile 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-ser495 (accessed [today's date]).

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