Is GCNT2 p.Cys72= (c.216C>T) pathogenic?

GCNT2 p.Cys72= (c.216C>T) is classified Benign in GCNT2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with cataract 13 with adult I phenotype.

What condition is associated with GCNT2 p.Cys72= (c.216C>T)?

GCNT2 p.Cys72= (c.216C>T) is associated with cataract 13 with adult I phenotype (ClinVar).

How is Early onset non-syndromic cataract inherited?

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

GCNT2 p.Cys72=

Q: How common is GCNT2 p.Cys72= (c.216C>T) in the general population?

GCNT2 p.Cys72= (c.216C>T) is common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.216C>T · rs2230906 · VCV258157

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 13.3%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

cataract 13 with adult I phenotype

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 0.17	GERP 0.77, phastCons 0.006
Overall
CADD	15.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.3% European (non-Finnish) · 157,431/1,179,644 alleles

Filtering AF 13.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.3%

Overall 12% 193,576/1,613,714 alleles · common exomes 178,565/1,461,500 · genomes 15,011/152,214 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	20%	5
Finnishnot grpmax-eligible	14.7%	7
Amishnot grpmax-eligible	13.5%	7
European (non-Finnish)grpmax	13.3%	7
Middle Eastern	12.1%	8
Remaining individualsnot grpmax-eligible	11.5%	9
South Asian	6.25%	16
Admixed American	5.05%	20
African / African-American	4.8%	21
East Asian	1.01%	99

Ashkenazi Jewish 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: GCNT2
Protein: p.Cys72=
Coding: c.216C>T
MANE Select: NM_145649 · reported on NM_001491
dbSNP: rs2230906
Type: single nucleotide variant
Location: chr6:10556639 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66

Full GCNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cataract 13 with adult I phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

GCNT2 p.Tyr349Cys Pathogenic/Likely pathogenic ★★ same condition
GCNT2 p.Lys135Glu Uncertain significance ★★ same condition
GCNT2 p.Val232Ile Uncertain significance ★★ ⚠ same condition
GCNT2 c.926-34546C>G Benign ★★ same condition
GCNT2 c.926-34857G>A Benign/Likely benign ★★ same condition
GCNT2 p.Ala247= Benign ★★ same condition
GCNT2 p.Arg110= Benign ★★ same condition
GCNT2 p.Arg173Gly Benign ★★ 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/gcnt2-p-cys72 (accessed [today's date]).

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