Is TNC p.Ala977Val (c.2930C>T) pathogenic?

TNC p.Ala977Val (c.2930C>T) is classified Uncertain significance in TNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.242); Very rare (popmax 0.004%, afr).

How common is TNC p.Ala977Val (c.2930C>T) in the general population?

TNC p.Ala977Val (c.2930C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about TNC p.Ala977Val (c.2930C>T)?

AlphaMissense predicts likely benign (score 0.242) — an in-silico prediction, not a clinical call.

TNC p.Ala977Val

c.2930C>T · VCV3808743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.242 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.242	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -5.48	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 12	GERP 2.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.8 · regional, not allelic
Overall
CADD	25.8	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 0.004% African / African-American · 3/75,020 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.00105% 17/1,614,070 alleles · very rare exomes 13/1,461,840 · genomes 4/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,007
Admixed American	0.00333%	30,010
South Asian	0.00329%	30,361
East Asian	0.00223%	44,866
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)	0.000593%	168,571

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.Ala977Val
Coding: c.2930C>T
MANE Select: NM_002160
Type: single nucleotide variant
Location: chr9:115076052 (GRCh38)
Gene constraint: LOEUF 0.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.48 · 21 PDB
Residue 977: the fibronectin type-iii 4 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-ala977val (accessed [today's date]).

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