Is GPC6 p.Pro20= (c.60C>T) pathogenic?

GPC6 p.Pro20= (c.60C>T) is classified Likely benign in GPC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). Very rare (popmax 0.00167%, amr).

How common is GPC6 p.Pro20= (c.60C>T) in the general population?

GPC6 p.Pro20= (c.60C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

GPC6 p.Pro20=

c.60C>T · rs1369671456 · VCV3008248

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.088	GERP -3.1, phastCons 0.03
Overall
CADD	8.601	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,028 alleles

Overall 0.000248% 4/1,613,876 alleles · very rare exomes 4/1,461,550 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,246
Admixed Americangrpmax	0.00167%	60,028
South Asian	0.0011%	91,082

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro20=
Coding: c.60C>T
MANE Select: NM_005708
dbSNP: rs1369671456
Type: single nucleotide variant
Location: chr13:93227516 (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

Similar variants

GPC6 p.Arg171Trp Pathogenic/Likely pathogenic ★★ same type
GPC6 p.Ala232Thr Uncertain significance ★★ same type
GPC6 p.Ala377Thr Uncertain significance ★★ ⚠ same type
GPC6 p.Ala519Thr Uncertain significance ★★ ⚠ same type
GPC6 p.Arg110Gln Uncertain significance ★★ ⚠ same type
GPC6 p.Arg126Trp Uncertain significance ★★ ⚠ same type
GPC6 p.Arg363His Uncertain significance ★★ same type
GPC6 p.Arg383Gln Uncertain significance ★★ ⚠ same type

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-pro20 (accessed [today's date]).

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