Is TANC2 p.Val549= (c.1647T>G) pathogenic?

TANC2 p.Val549= (c.1647T>G) is classified Likely benign in TANC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Ultra-rare (popmax 0.045%, amr).

How common is TANC2 p.Val549= (c.1647T>G) in the general population?

TANC2 p.Val549= (c.1647T>G) is ultra-rare (popmax 0.045%, amr) (gnomAD).

TANC2 p.Val549=

c.1647T>G · VCV4874257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.6, phastCons 0.001
Overall
CADD	6.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% Admixed American · 27/60,002 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00248% 40/1,613,850 alleles · ultra-rare exomes 30/1,461,700 · genomes 10/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.045%	2,222
Remaining individualsnot grpmax-eligible	0.0064%	15,616
African / African-American	0.00267%	37,454
European (non-Finnish)	0.000593%	168,558

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: TANC2
Protein: p.Val549=
Coding: c.1647T>G
MANE Select: NM_001394998
Type: single nucleotide variant
Location: chr17:63340172 (GRCh38)
Gene constraint: LOEUF 0.17 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.92

Full TANC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TANC2 p.Arg1516Gln Uncertain significance ★★ ⚠ same type
TANC2 p.Arg1741Gln Uncertain significance ★★ ⚠ same type
TANC2 p.Arg1923Ter Uncertain significance ★★ same type
TANC2 p.Arg268Cys Uncertain significance ★★ ⚠ same type
TANC2 p.Arg388His Uncertain significance ★★ ⚠ same type
TANC2 p.Arg466Lys Uncertain significance ★★ ⚠ same type
TANC2 p.Arg563Trp Uncertain significance ★★ ⚠ same type
TANC2 p.Arg834Cys 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/tanc2-p-val549 (accessed [today's date]).

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