Is GLMN p.Ala32Val (c.95C>T) pathogenic?

GLMN p.Ala32Val (c.95C>T) is classified Uncertain significance in GLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: ambiguous (0.4211); Ultra-rare (popmax 0.0499%, mid); Associated with Inborn genetic diseases.

What condition is associated with GLMN p.Ala32Val (c.95C>T)?

GLMN p.Ala32Val (c.95C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GLMN p.Ala32Val (c.95C>T) in the general population?

GLMN p.Ala32Val (c.95C>T) is ultra-rare (popmax 0.0499%, mid) (gnomAD).

What do computational predictors say about GLMN p.Ala32Val (c.95C>T)?

AlphaMissense predicts ambiguous (score 0.4211) — an in-silico prediction, not a clinical call.

GLMN p.Ala32Val

c.95C>T · VCV3854279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4211 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0499%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4211	ambiguous
REVEL	0.258	benign-leaning
SaProt	LLR -9.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	24.9	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 0.0499% Middle Eastern · 3/6,008 alleles

Filtering AF 0.015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0142%

Overall 0.0151% 243/1,609,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0811%	1,233
Middle Easterngrpmax	0.0499%	2,003
European (non-Finnish)	0.0169%	5,924
Remaining individualsnot grpmax-eligible	0.016%	6,243
South Asian	0.0055%	18,197
East Asian	0.00223%	44,758
Admixed American	0.00168%	59,610

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala32Val
Coding: c.95C>T
MANE Select: NM_053274
Type: single nucleotide variant
Location: chr1:92297474 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 32: an α-helix; the 'alpha-helical region with structural similarity to heat repeats' 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.Arg12Lys 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-ala32val (accessed [today's date]).

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