Is TG p.Met1826Val (c.5476A>G) pathogenic?

TG p.Met1826Val (c.5476A>G) is classified Uncertain significance in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: likely benign (0.099); Ultra-rare (popmax 0.0147%, afr); Associated with Inborn genetic diseases.

What condition is associated with TG p.Met1826Val (c.5476A>G)?

TG p.Met1826Val (c.5476A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TG p.Met1826Val (c.5476A>G) in the general population?

TG p.Met1826Val (c.5476A>G) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

What do computational predictors say about TG p.Met1826Val (c.5476A>G)?

AlphaMissense predicts likely benign (score 0.099) — an in-silico prediction, not a clinical call.

TG p.Met1826Val

c.5476A>G · rs377106482 · VCV2227448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.099	likely benign
REVEL	0.378	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	16.48	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 0.0147% African / African-American · 11/74,858 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00634%

Overall 0.000682% 11/1,613,750 alleles · ultra-rare exomes 0/1,461,662 · genomes 11/152,088 · 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.Met1826Val
Coding: c.5476A>G
MANE Select: NM_003235
dbSNP: rs377106482
Type: single nucleotide variant
Location: chr8:132963002 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 1826: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TG p.Ala1033Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1419Glu Uncertain significance ★★ same condition
TG p.Ala1419Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1583Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1631Ser Uncertain significance ★★ ⚠ same condition
TG p.Ala402Gly Uncertain significance ★★ ⚠ same condition
TG p.Ala457Val Uncertain significance ★★ same condition
TG p.Arg1066Cys Uncertain significance ★★ same condition

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-met1826val (accessed [today's date]).

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