Is TEC p.Val426Met (c.1276G>A) pathogenic?

TEC p.Val426Met (c.1276G>A) is classified Uncertain significance in TEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely pathogenic (0.978); Very rare (popmax 0.00288%, nfe).

How common is TEC p.Val426Met (c.1276G>A) in the general population?

TEC p.Val426Met (c.1276G>A) is very rare (popmax 0.00288%, nfe) (gnomAD).

What do computational predictors say about TEC p.Val426Met (c.1276G>A)?

AlphaMissense predicts likely pathogenic (score 0.978) — an in-silico prediction, not a clinical call.

TEC p.Val426Met

c.1276G>A · VCV3966891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.978	likely pathogenic
REVEL	0.757	pathogenic-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 12 kb · p 3.1e-07 · regional, not allelic
Overall
CADD	28.0	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 0.00288% European (non-Finnish) · 34/1,180,002 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00223% 36/1,614,044 alleles · very rare exomes 36/1,461,854 · genomes 0/152,190 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)grpmax	0.00288%	34,706

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val426Met
Coding: c.1276G>A
MANE Select: NM_003215
Type: single nucleotide variant
Location: chr4:48145273 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 1 PDB
Residue 426: the protein kinase 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-val426met (accessed [today's date]).

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