Is TEC p.Gln131Arg (c.392A>G) pathogenic?

TEC p.Gln131Arg (c.392A>G) is classified Uncertain significance in TEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.1064); Ultra-rare (popmax 0.0506%, mid).

How common is TEC p.Gln131Arg (c.392A>G) in the general population?

TEC p.Gln131Arg (c.392A>G) is ultra-rare (popmax 0.0506%, mid) (gnomAD).

What do computational predictors say about TEC p.Gln131Arg (c.392A>G)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

TEC p.Gln131Arg

c.392A>G · VCV4182094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0506%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.644	pathogenic-leaning
SaProt	LLR -8.60	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 79 kb · p 0.38 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0506% Middle Eastern · 3/5,924 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00734%

Overall 0.00404% 63/1,561,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0506%	1,975
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,759
Remaining individualsnot grpmax-eligible	0.0099%	10,106
Admixed American	0.00669%	14,953
European (non-Finnish)	0.00388%	25,761
African / African-American	0.0027%	36,989
South Asian	0.00113%	88,726

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.Gln131Arg
Coding: c.392A>G
MANE Select: NM_003215
Type: single nucleotide variant
Location: chr4:48170310 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.48 · 1 PDB

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-gln131arg (accessed [today's date]).

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