Is GLS p.Ser77Pro (c.229T>C) pathogenic?

GLS p.Ser77Pro (c.229T>C) is classified Uncertain significance in GLS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely benign (0.0782); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GLS p.Ser77Pro (c.229T>C)?

GLS p.Ser77Pro (c.229T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GLS p.Ser77Pro (c.229T>C) in the general population?

GLS p.Ser77Pro (c.229T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLS p.Ser77Pro (c.229T>C)?

AlphaMissense predicts likely benign (score 0.0782) — an in-silico prediction, not a clinical call.

GLS p.Ser77Pro

c.229T>C · rs1367964499 · VCV2304627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0782 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,512,248)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0782	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.2, phastCons 1
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,512,248). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GLS
Protein: p.Ser77Pro
Coding: c.229T>C
MANE Select: NM_014905
dbSNP: rs1367964499
Type: single nucleotide variant
Location: chr2:190881313 (GRCh38)
Structure: AlphaFold pLDDT 85.66 · 4 PDB
Residue 77: an α-helix

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.Ser77= Likely benign ★ same residue
GLS p.Ser77Ala 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

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-ser77pro (accessed [today's date]).

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