Is TKT p.Ala403= (c.1209C>G) pathogenic?

TKT p.Ala403= (c.1209C>G) is classified Benign/Likely benign in TKT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-12). Rare (popmax 0.419%, afr).

How common is TKT p.Ala403= (c.1209C>G) in the general population?

TKT p.Ala403= (c.1209C>G) is rare (popmax 0.419%, afr) (gnomAD).

TKT p.Ala403=

c.1209C>G · rs144151385 · VCV717183

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.419%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.5
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.419% African / African-American · 314/74,998 alleles

Filtering AF 0.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.366%

Overall 0.0208% 336/1,613,966 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.419%	239
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Admixed American	0.0167%	6,000
European (non-Finnish)	8.47e-05%	1,179,965

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: TKT
Protein: p.Ala403=
Coding: c.1209C>G
MANE Select: NM_001064
dbSNP: rs144151385
Type: single nucleotide variant
Location: chr3:53229335 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.11 · 13 PDB
Residue 403: an α-helix

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

Similar variants

TKT p.Arg591Trp Uncertain significance ★★ ⚠ same type
TKT p.Asp106Tyr Uncertain significance ★★ ⚠ same type
TKT p.Leu153Pro Uncertain significance ★★ ⚠ same type
TKT p.Leu98Pro Uncertain significance ★★ ⚠ same type
TKT p.Tyr202Cys Uncertain significance ★★ same type
TKT c.1264+17T>C Benign ★★ same type
TKT c.1265-47G>C Benign ★★ same type
TKT c.1697-49C>T Benign ★★ 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/tkt-p-ala403 (accessed [today's date]).

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