Is GLS p.Ser482Cys (c.1445C>G) pathogenic?

GLS p.Ser482Cys (c.1445C>G) is classified Pathogenic in GLS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely pathogenic (0.9792); Absent from gnomAD v4.1; Associated with infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development.

How common is GLS p.Ser482Cys (c.1445C>G) in the general population?

GLS p.Ser482Cys (c.1445C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLS p.Ser482Cys (c.1445C>G)?

AlphaMissense predicts likely pathogenic (score 0.9792) — an in-silico prediction, not a clinical call.

GLS p.Ser482Cys

Q: What condition is associated with GLS p.Ser482Cys (c.1445C>G)?

GLS p.Ser482Cys (c.1445C>G) is associated with infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development (ClinVar).

c.1445C>G · rs1558986214 · VCV619106

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development

Computational evidence

Protein change
AlphaMissense	0.9792	likely pathogenic ✓ concordant with ClinVar
REVEL	0.747	pathogenic-leaning
SaProt	LLR -11.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GLS
Protein: p.Ser482Cys
Coding: c.1445C>G
MANE Select: NM_014905
dbSNP: rs1558986214
Type: single nucleotide variant
Location: chr2:190930456 (GRCh38)
Structure: AlphaFold pLDDT 85.66 · 4 PDB

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

Disease context

infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GLS p.Lys289Ile Likely pathogenic ★ same condition
GLS p.Ala473Val Uncertain significance ★ ⚠ same condition
GLS p.Met508Lys Uncertain significance ★ ⚠ same condition
GLS p.His461Leu Pathogenic same condition
GLS p.Ala99Thr Uncertain significance ★★ ⚠ same type
GLS p.Leu25Arg Uncertain significance ★★ ⚠ same type
GLS c.387-3T>C Likely benign ★★ same type
GLS p.Ala561= Benign ★★ 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/gls-p-ser482cys (accessed [today's date]).

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