Is TGOLN2 p.Ala397Val (c.1190C>T) pathogenic?

TGOLN2 p.Ala397Val (c.1190C>T) is classified Uncertain significance in TGOLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely pathogenic (0.8444); Absent from gnomAD v4.1.

How common is TGOLN2 p.Ala397Val (c.1190C>T) in the general population?

TGOLN2 p.Ala397Val (c.1190C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGOLN2 p.Ala397Val (c.1190C>T)?

AlphaMissense predicts likely pathogenic (score 0.8444) — an in-silico prediction, not a clinical call.

TGOLN2 p.Ala397Val

c.1190C>T · VCV4183759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8444 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8444	likely pathogenic · top 7% in TGOLN2
REVEL	0.233	benign-leaning
SaProt	LLR -10.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 5,223 bp · p 0.42 · regional, not allelic
Overall
CADD	28.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TGOLN2
Protein: p.Ala397Val
Coding: c.1190C>T
MANE Select: NM_006464
Type: single nucleotide variant
Location: chr2:85326542 (GRCh38)
Gene constraint: LOEUF 0.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.67 · 1 PDB

Full TGOLN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TGOLN2 c.*42T>C Uncertain significance ★ same type
TGOLN2 c.*51C>G Uncertain significance ★ same type
TGOLN2 p.Ala13Val Uncertain significance ★ ⚠ same type
TGOLN2 p.Ala22Val Uncertain significance ★ ⚠ same type
TGOLN2 p.Ala393Gly Uncertain significance ★ ⚠ same type
TGOLN2 p.Ala6Val Uncertain significance ★ ⚠ same type
TGOLN2 p.Arg259Pro Uncertain significance ★ ⚠ same type
TGOLN2 p.Arg407Gln 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/tgoln2-p-ala397val (accessed [today's date]).

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