Is TNC p.Val1342Phe (c.4024G>T) pathogenic?

TNC p.Val1342Phe (c.4024G>T) is classified Uncertain significance in TNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.1784); Very rare (popmax 0.00223%, eas).

How common is TNC p.Val1342Phe (c.4024G>T) in the general population?

TNC p.Val1342Phe (c.4024G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about TNC p.Val1342Phe (c.4024G>T)?

AlphaMissense predicts likely benign (score 0.1784) — an in-silico prediction, not a clinical call.

TNC p.Val1342Phe

c.4024G>T · VCV4187780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1784	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -12.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 0.96, phastCons 0.11
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.8 · regional, not allelic
Overall
CADD	13.77	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 0.00223% East Asian · 1/44,858 alleles

Overall 6.2e-05% 1/1,613,300 alleles · very rare exomes 1/1,461,066 · genomes 0/152,234 · joint denominator

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: TNC
Protein: p.Val1342Phe
Coding: c.4024G>T
MANE Select: NM_002160
Type: single nucleotide variant
Location: chr9:115062926 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 1342: the fibronectin type-iii 8 domain

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

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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/tnc-p-val1342phe (accessed [today's date]).

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