Is TG p.Ala2522Pro (c.7564G>C) pathogenic?

TG p.Ala2522Pro (c.7564G>C) is classified Uncertain significance in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). AlphaMissense: likely pathogenic (0.8666); Very rare (popmax 0.000339%, nfe).

How common is TG p.Ala2522Pro (c.7564G>C) in the general population?

TG p.Ala2522Pro (c.7564G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about TG p.Ala2522Pro (c.7564G>C)?

AlphaMissense predicts likely pathogenic (score 0.8666) — an in-silico prediction, not a clinical call.

TG p.Ala2522Pro

c.7564G>C · rs747745496 · VCV2658843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8666 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.8666	likely pathogenic
REVEL	0.36	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.21	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,030 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,146 alleles · very rare exomes 4/1,461,870 · genomes 0/152,276 · 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.Ala2522Pro
Coding: c.7564G>C
MANE Select: NM_003235
dbSNP: rs747745496
Type: single nucleotide variant
Location: chr8:133096365 (GRCh38)

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

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-ala2522pro (accessed [today's date]).

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