Is TGOLN2 p.Ala6Val (c.17C>T) pathogenic?

TGOLN2 p.Ala6Val (c.17C>T) is classified Uncertain significance in TGOLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2071); Rare (popmax 0.278%, afr).

How common is TGOLN2 p.Ala6Val (c.17C>T) in the general population?

TGOLN2 p.Ala6Val (c.17C>T) is rare (popmax 0.278%, afr) (gnomAD).

What do computational predictors say about TGOLN2 p.Ala6Val (c.17C>T)?

AlphaMissense predicts likely benign (score 0.2071) — an in-silico prediction, not a clinical call.

TGOLN2 p.Ala6Val

c.17C>T · VCV4183758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2071 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.278%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2071	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -0.2
Regional constraint	o/e 0.97	unconstrained · MANE · 5,223 bp · p 0.42 · regional, not allelic
Overall
CADD	15.09	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

Grpmax group 0.278% African / African-American · 208/74,868 alleles

Filtering AF 0.247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.235%

Overall 0.0136% 218/1,601,308 alleles · rare exomes 119/1,449,054 · genomes 99/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.278%	360
Admixed American	0.00856%	11,686
Remaining individualsnot grpmax-eligible	0.00807%	12,396

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: TGOLN2
Protein: p.Ala6Val
Coding: c.17C>T
MANE Select: NM_006464
Type: single nucleotide variant
Location: chr2:85327946 (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.Ala397Val 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-ala6val (accessed [today's date]).

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