Is GLMN p.Phe563Ser (c.1688T>C) pathogenic?

GLMN p.Phe563Ser (c.1688T>C) is classified Uncertain significance in GLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.5642); Ultra-rare (popmax 0.0202%, afr); Associated with Inborn genetic diseases.

What condition is associated with GLMN p.Phe563Ser (c.1688T>C)?

GLMN p.Phe563Ser (c.1688T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GLMN p.Phe563Ser (c.1688T>C) in the general population?

GLMN p.Phe563Ser (c.1688T>C) is ultra-rare (popmax 0.0202%, afr) (gnomAD).

What do computational predictors say about GLMN p.Phe563Ser (c.1688T>C)?

AlphaMissense predicts likely pathogenic (score 0.5642) — an in-silico prediction, not a clinical call.

GLMN p.Phe563Ser

c.1688T>C · rs761180709 · VCV2207151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5642	likely pathogenic
REVEL	0.222	benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP -0.51, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0202% African / African-American · 15/74,264 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00997%

Overall 0.00152% 24/1,579,542 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0202%	4,951
Admixed American	0.00501%	19,975
Remaining individualsnot grpmax-eligible	0.00488%	20,474
South Asian	0.00332%	30,129

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.Phe563Ser
Coding: c.1688T>C
MANE Select: NM_053274
dbSNP: rs761180709
Type: single nucleotide variant
Location: chr1:92246627 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 563: 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

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-phe563ser (accessed [today's date]).

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