Is GLMN p.Pro365Ser (c.1093C>T) pathogenic?

GLMN p.Pro365Ser (c.1093C>T) is classified Uncertain significance in GLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1987); Absent from gnomAD v4.1; Associated with glomuvenous malformation.

What condition is associated with GLMN p.Pro365Ser (c.1093C>T)?

GLMN p.Pro365Ser (c.1093C>T) is associated with glomuvenous malformation (ClinVar).

How common is GLMN p.Pro365Ser (c.1093C>T) in the general population?

GLMN p.Pro365Ser (c.1093C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLMN p.Pro365Ser (c.1093C>T)?

AlphaMissense predicts likely benign (score 0.1987) — an in-silico prediction, not a clinical call.

GLMN p.Pro365Ser

c.1093C>T · rs1655830610 · VCV873605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glomuvenous malformation

Computational evidence

Protein change
AlphaMissense	0.1987	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -10.09	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	22.3	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: GLMN
Protein: p.Pro365Ser
Coding: c.1093C>T
MANE Select: NM_053274
dbSNP: rs1655830610
Type: single nucleotide variant
Location: chr1:92267918 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 365: the 'alpha-helical region with structural similarity to heat repeats' region; the 'important for interaction with rbx1' region; an α-helix

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

Disease context

glomuvenous malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GLMN p.Cys36Ter Pathogenic/Likely pathogenic ★★ same condition
GLMN p.Ala140Pro Uncertain significance ★★ ⚠ same condition
GLMN p.Ala146Val Uncertain significance ★★ ⚠ same condition
GLMN p.Ser411Thr Uncertain significance ★★ ⚠ same condition
GLMN p.Val191Phe Uncertain significance ★★ ⚠ same condition
GLMN c.165+10A>G Benign/Likely benign ★★ same condition
GLMN c.977+7T>A Benign ★★ same condition
GLMN c.977+9G>A 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/glmn-p-pro365ser (accessed [today's date]).

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