Is TG p.Ala2626Val (c.7877C>T) pathogenic?

TG p.Ala2626Val (c.7877C>T) is classified Uncertain significance in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1165); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with TG p.Ala2626Val (c.7877C>T)?

TG p.Ala2626Val (c.7877C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TG p.Ala2626Val (c.7877C>T) in the general population?

TG p.Ala2626Val (c.7877C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about TG p.Ala2626Val (c.7877C>T)?

AlphaMissense predicts likely benign (score 0.1165) — an in-silico prediction, not a clinical call.

TG p.Ala2626Val

c.7877C>T · rs1321536850 · VCV2469656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1165	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.3, phastCons 0.62
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	11.62	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,916 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00192% 31/1,614,058 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,458
European (non-Finnish)	0.00237%	42,144
South Asian	0.0011%	91,088

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.Ala2626Val
Coding: c.7877C>T
MANE Select: NM_003235
dbSNP: rs1321536850
Type: single nucleotide variant
Location: chr8:133131826 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 2626: a UniProt-annotated variant site (in tdh3; uncertain significance); the 'cholinesterase-like (chel)' region; an α-helix

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.Ala2626Glu Uncertain significance ★ ⚠ same residue
TG p.Ala2626= Likely benign ★ same residue
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

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-ala2626val (accessed [today's date]).

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