Is GLMN p.Pro547Ser (c.1639C>T) pathogenic?

GLMN p.Pro547Ser (c.1639C>T) is classified Uncertain significance in GLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely benign (0.1217); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with GLMN p.Pro547Ser (c.1639C>T)?

GLMN p.Pro547Ser (c.1639C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GLMN p.Pro547Ser (c.1639C>T) in the general population?

GLMN p.Pro547Ser (c.1639C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about GLMN p.Pro547Ser (c.1639C>T)?

AlphaMissense predicts likely benign (score 0.1217) — an in-silico prediction, not a clinical call.

GLMN p.Pro547Ser

c.1639C>T · rs191480502 · VCV2536880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1217 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1217	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	22.1	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

Grpmax group 0.01% Admixed American · 6/59,948 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000381% 6/1,574,882 alleles · ultra-rare

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: GLMN
Protein: p.Pro547Ser
Coding: c.1639C>T
MANE Select: NM_053274
dbSNP: rs191480502
Type: single nucleotide variant
Location: chr1:92247091 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 547: the 'alpha-helical region with structural similarity to heat repeats' region; the 'important for interaction with rbx1' region

Full GLMN 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

GLMN c.1214+2T>C Pathogenic/Likely pathogenic ★★ same condition
GLMN p.Ala140Pro Uncertain significance ★★ ⚠ same condition
GLMN p.Ala146Val Uncertain significance ★★ ⚠ same condition
GLMN p.Gln117Glu Uncertain significance ★★ ⚠ same condition
GLMN p.Met168Val Uncertain significance ★★ ⚠ same condition
GLMN p.Ser411Thr Uncertain significance ★★ ⚠ same condition
GLMN p.Val191Phe Uncertain significance ★★ ⚠ same condition
GLMN p.Ala32Val 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/glmn-p-pro547ser (accessed [today's date]).

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