Is TG p.Ala397= (c.1191C>T) pathogenic?

TG p.Ala397= (c.1191C>T) is classified Likely benign in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Very rare (popmax 0.000424%, nfe).

How common is TG p.Ala397= (c.1191C>T) in the general population?

TG p.Ala397= (c.1191C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

TG p.Ala397=

c.1191C>T · VCV3618217

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.46	GERP -1.9
Overall
CADD	1.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,032 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,208 alleles · very rare exomes 5/1,461,894 · genomes 0/152,314 · joint denominator

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: TG
Protein: p.Ala397=
Coding: c.1191C>T
MANE Select: NM_003235
Type: single nucleotide variant
Location: chr8:132886563 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)

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

Similar variants

TG p.Ala397Asp Uncertain significance ★ ⚠ same residue
TG c.274+1G>A Pathogenic ★★ same type
TG c.274+2T>G Pathogenic ★★ same type
TG c.3634+1G>A Likely pathogenic ★★ same type
TG c.4528+1G>A Pathogenic/Likely pathogenic ★★ same type
TG c.5686+1G>A Pathogenic ★★ same type
TG c.5686+1G>T Pathogenic ★★ same type
TG c.638+5G>A Pathogenic/Likely pathogenic ★★ 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/tg-p-ala397 (accessed [today's date]).

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