Is TEC p.Lys266Thr (c.797A>C) pathogenic?

TEC p.Lys266Thr (c.797A>C) is classified Uncertain significance in TEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely pathogenic (0.9488); Very rare (popmax 8.58e-05%, nfe).

How common is TEC p.Lys266Thr (c.797A>C) in the general population?

TEC p.Lys266Thr (c.797A>C) is very rare (popmax 8.58e-05%, nfe) (gnomAD).

What do computational predictors say about TEC p.Lys266Thr (c.797A>C)?

AlphaMissense predicts likely pathogenic (score 0.9488) — an in-silico prediction, not a clinical call.

TEC p.Lys266Thr

c.797A>C · VCV3966890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9488 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.58e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9488	likely pathogenic
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -12.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.51 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 79 kb · p 0.38 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.58e-05% European (non-Finnish) · 1/1,165,608 alleles

Overall 6.99e-05% 1/1,430,052 alleles · very rare

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: TEC
Protein: p.Lys266Thr
Coding: c.797A>C
MANE Select: NM_003215
Type: single nucleotide variant
Location: chr4:48150938 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 1 PDB
Residue 266: the sh2 domain

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

Similar variants

TEC c.496-1G>A Likely pathogenic ★ same type
TEC p.Ala500Val Uncertain significance ★ ⚠ same type
TEC p.Arg202Ser Uncertain significance ★ ⚠ same type
TEC p.Arg262Leu Uncertain significance ★ ⚠ same type
TEC p.Arg29Gly Uncertain significance ★ ⚠ same type
TEC p.Arg342Gln Uncertain significance ★ ⚠ same type
TEC p.Arg390Gln Uncertain significance ★ same type
TEC p.Arg617Cys Uncertain significance ★ ⚠ 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/tec-p-lys266thr (accessed [today's date]).

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