Is TNC p.Ser413Asn (c.1238G>A) pathogenic?

TNC p.Ser413Asn (c.1238G>A) is classified Uncertain significance in TNC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-02). AlphaMissense: likely benign (0.1452); Absent from gnomAD v4.1.

How common is TNC p.Ser413Asn (c.1238G>A) in the general population?

TNC p.Ser413Asn (c.1238G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TNC p.Ser413Asn (c.1238G>A)?

AlphaMissense predicts likely benign (score 0.1452) — an in-silico prediction, not a clinical call.

TNC p.Ser413Asn

c.1238G>A · VCV4904313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1452 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1452	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.45
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.8 · regional, not allelic
Overall
CADD	12.06	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TNC
Protein: p.Ser413Asn
Coding: c.1238G>A
MANE Select: NM_002160
Type: single nucleotide variant
Location: chr9:115086493 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 413: the egf-like 9 domain

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

Similar variants

TNC p.Arg1127Trp Uncertain significance ★★ ⚠ same type
TNC p.Arg608Cys Uncertain significance ★★ ⚠ same type
TNC p.Arg669His Uncertain significance ★★ ⚠ same type
TNC p.Arg747Trp Uncertain significance ★★ ⚠ same type
TNC p.Asn507Lys Uncertain significance ★★ ⚠ same type
TNC p.Asp2059Glu Uncertain significance ★★ ⚠ same type
TNC p.Asp831Asn Uncertain significance ★★ ⚠ same type
TNC p.Asp971Asn 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/tnc-p-ser413asn (accessed [today's date]).

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