Is GCNT2 p.Arg385= (c.1155C>T) pathogenic?

GCNT2 p.Arg385= (c.1155C>T) is classified Likely benign in GCNT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). Ultra-rare (popmax 0.0483%, amr); Associated with cataract 13 with adult I phenotype.

What condition is associated with GCNT2 p.Arg385= (c.1155C>T)?

GCNT2 p.Arg385= (c.1155C>T) is associated with cataract 13 with adult I phenotype (ClinVar).

How common is GCNT2 p.Arg385= (c.1155C>T) in the general population?

GCNT2 p.Arg385= (c.1155C>T) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

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.Arg385=

c.1155C>T · rs370574556 · VCV1092022

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

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 0.047	GERP -3.4, phastCons 0.083
Overall
CADD	7.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/60,022 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.0083% 134/1,613,772 alleles · ultra-rare exomes 114/1,461,572 · genomes 20/152,200 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.00797%	12,550
East Asian	0.00446%	22,440

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.Arg385=
Coding: c.1155C>T
MANE Select: NM_145649
dbSNP: rs370574556
Type: single nucleotide variant
Location: chr6:10626553 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66
Residue 385: a UniProt-annotated variant site (in ctrct13; uncertain significance)

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.Arg385His Conflicting classifications of pathogenicity ★ ⚠ same residue
GCNT2 p.Arg385Cys Uncertain significance ★ ⚠ same residue
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

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-arg385 (accessed [today's date]).

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