Is GLS p.Ser264Pro (c.790T>C) pathogenic?

GLS p.Ser264Pro (c.790T>C) is classified Uncertain significance in GLS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GLS p.Ser264Pro (c.790T>C)?

GLS p.Ser264Pro (c.790T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GLS p.Ser264Pro (c.790T>C) in the general population?

GLS p.Ser264Pro (c.790T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLS p.Ser264Pro (c.790T>C)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

GLS p.Ser264Pro

c.790T>C · VCV3520677

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 1% in GLS
REVEL	0.555	indeterminate
SaProt	LLR -13.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ser264Pro
Coding: c.790T>C
MANE Select: NM_013267 · reported on NM_014905
Type: single nucleotide variant
Location: chr2:190902001 (GRCh38)
Structure: AlphaFold pLDDT 85.66 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GLS p.Ser264Thr Uncertain significance ★ ⚠ same residue
GLS p.Ala99Thr Uncertain significance ★★ ⚠ same condition
GLS p.Leu25Arg Uncertain significance ★★ ⚠ same condition
GLS p.Arg570Gln Likely pathogenic ★ same condition
GLS p.Ala23Thr Uncertain significance ★ ⚠ same condition
GLS p.Ala28Thr Uncertain significance ★ ⚠ same condition
GLS p.Ala50Asp Uncertain significance ★ ⚠ same condition
GLS p.Ala50Thr 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/gls-p-ser264pro (accessed [today's date]).

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