Is TNC p.Val37Met (c.109G>A) pathogenic?

TNC p.Val37Met (c.109G>A) is classified Conflicting classifications of pathogenicity in TNC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0798); Ultra-rare (popmax 0.084%, afr).

How common is TNC p.Val37Met (c.109G>A) in the general population?

TNC p.Val37Met (c.109G>A) is ultra-rare (popmax 0.084%, afr) (gnomAD).

What do computational predictors say about TNC p.Val37Met (c.109G>A)?

AlphaMissense predicts likely benign (score 0.0798) — an in-silico prediction, not a clinical call.

TNC p.Val37Met

c.109G>A · rs139580620 · VCV1317958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0798 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.084%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0798	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -8.94	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 -1.2	GERP -2.2
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.8 · regional, not allelic
Overall
CADD	9.029	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 0.084% African / African-American · 63/75,020 alleles

Filtering AF 0.0674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.00415% 67/1,614,142 alleles · ultra-rare exomes 38/1,461,888 · genomes 29/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.084%	1,191
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00167%	60,024

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.Val37Met
Coding: c.109G>A
MANE Select: NM_002160
dbSNP: rs139580620
Type: single nucleotide variant
Location: chr9:115090910 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB

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-val37met (accessed [today's date]).

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