Is TECPR2 p.Val1126Ala (c.3377T>C) pathogenic?

TECPR2 p.Val1126Ala (c.3377T>C) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: ambiguous (0.4584); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with TECPR2 p.Val1126Ala (c.3377T>C)?

TECPR2 p.Val1126Ala (c.3377T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TECPR2 p.Val1126Ala (c.3377T>C) in the general population?

TECPR2 p.Val1126Ala (c.3377T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about TECPR2 p.Val1126Ala (c.3377T>C)?

AlphaMissense predicts ambiguous (score 0.4584) — an in-silico prediction, not a clinical call.

TECPR2 p.Val1126Ala

c.3377T>C · rs1267728416 · VCV3175636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4584	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -8.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	24.9	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 0.0011% South Asian · 1/91,084 alleles

Overall 0.000124% 2/1,614,212 alleles · very rare exomes 2/1,461,874 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,180,018

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: TECPR2
Protein: p.Val1126Ala
Coding: c.3377T>C
MANE Select: NM_014844
dbSNP: rs1267728416
Type: single nucleotide variant
Location: chr14:102450620 (GRCh38)
Gene constraint: LOEUF 0.607 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.27

Full TECPR2 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

TECPR2 p.Val1126= Likely benign ★ same residue
TECPR2 p.Ala1176Thr Uncertain significance ★★ ⚠ same condition
TECPR2 p.Ala380Val Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg1066Cys Uncertain significance ★★ same condition
TECPR2 p.Arg273His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg32His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg716His Uncertain significance ★★ ⚠ same condition
TECPR2 p.Arg943Trp 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/tecpr2-p-val1126ala (accessed [today's date]).

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