Is GLMN p.Val191Phe (c.571G>T) pathogenic?

GLMN p.Val191Phe (c.571G>T) is classified Uncertain significance in GLMN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-03). AlphaMissense: likely benign (0.2405); Ultra-rare (popmax 0.0483%, amr); Associated with Inborn genetic diseases.

What condition is associated with GLMN p.Val191Phe (c.571G>T)?

GLMN p.Val191Phe (c.571G>T) is associated with Inborn genetic diseases, glomuvenous malformation (ClinVar).

How common is GLMN p.Val191Phe (c.571G>T) in the general population?

GLMN p.Val191Phe (c.571G>T) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about GLMN p.Val191Phe (c.571G>T)?

AlphaMissense predicts likely benign (score 0.2405) — an in-silico prediction, not a clinical call.

GLMN p.Val191Phe

c.571G>T · rs199528216 · VCV2561250

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2405 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2405	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -10.44	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 0.87	GERP 0.42, phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	22.2	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 0.0483% Admixed American · 29/59,996 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.0137% 221/1,612,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,069
Remaining individualsnot grpmax-eligible	0.024%	4,163
European (non-Finnish)	0.0144%	6,934
East Asian	0.0111%	8,969
African / African-American	0.00267%	37,508

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.Val191Phe
Coding: c.571G>T
MANE Select: NM_053274
dbSNP: rs199528216
Type: single nucleotide variant
Location: chr1:92288975 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 191: the 'alpha-helical region with structural similarity to heat repeats' 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

Also linked: glomuvenous malformation

Similar variants

GLMN c.1214+2T>C Pathogenic/Likely pathogenic ★★ same condition
GLMN p.Cys36Ter 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 c.165+10A>G Benign/Likely 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-val191phe (accessed [today's date]).

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