Is GLMN p.Ala460Val (c.1379C>T) pathogenic?

GLMN p.Ala460Val (c.1379C>T) is classified Uncertain significance in GLMN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). AlphaMissense: likely benign (0.1182); Absent from gnomAD v4.1.

How common is GLMN p.Ala460Val (c.1379C>T) in the general population?

GLMN p.Ala460Val (c.1379C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GLMN p.Ala460Val (c.1379C>T)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

GLMN p.Ala460Val

c.1379C>T · VCV4541298

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,573,182)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	donor loss, 30 bp away · masked 0 · deltas
Pangolin	Δ0.32	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 51 kb · p 0.0058 · regional, not allelic
Overall
CADD	21.2	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

No allele count reported in gnomAD v4.1 (AN 1,573,182). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GLMN
Protein: p.Ala460Val
Coding: c.1379C>T
MANE Select: NM_053274
Type: single nucleotide variant
Location: chr1:92263653 (GRCh38)
Gene constraint: LOEUF 1.705 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 1 PDB
Residue 460: the 'alpha-helical region with structural similarity to heat repeats' region; the 'important for interaction with rbx1' region; a turn

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

Similar variants

GLMN c.1214+2T>C Pathogenic/Likely pathogenic ★★ same type
GLMN p.Arg574Ter Likely pathogenic ★★ same type
GLMN p.Cys36Ter Pathogenic/Likely pathogenic ★★ same type
GLMN p.Ala140Pro Uncertain significance ★★ ⚠ same type
GLMN p.Ala146Val Uncertain significance ★★ ⚠ same type
GLMN p.Gln117Glu Uncertain significance ★★ ⚠ same type
GLMN p.Met168Val Uncertain significance ★★ ⚠ same type
GLMN p.Ser411Thr Uncertain significance ★★ ⚠ same type

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-ala460val (accessed [today's date]).

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