Is TECPR2 p.Ile349Val (c.1045A>G) pathogenic?

TECPR2 p.Ile349Val (c.1045A>G) is classified Uncertain significance in TECPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.2025); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with TECPR2 p.Ile349Val (c.1045A>G)?

TECPR2 p.Ile349Val (c.1045A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TECPR2 p.Ile349Val (c.1045A>G) in the general population?

TECPR2 p.Ile349Val (c.1045A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about TECPR2 p.Ile349Val (c.1045A>G)?

AlphaMissense predicts likely benign (score 0.2025) — an in-silico prediction, not a clinical call.

TECPR2 p.Ile349Val

c.1045A>G · VCV3454613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2025 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2025	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 122 kb · p 2.1e-10 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,074 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.000621% 10/1,610,422 alleles · ultra-rare exomes 9/1,460,258 · genomes 1/150,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,074
East Asian	0.0112%	8,952
Remaining individualsnot grpmax-eligible	0.0032%	31,202
European (non-Finnish)	0.00017%	589,699

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.Ile349Val
Coding: c.1045A>G
MANE Select: NM_014844
Type: single nucleotide variant
Location: chr14:102428343 (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

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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
TECPR2 p.Asp1021Asn 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-ile349val (accessed [today's date]).

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