Is TANC2 p.Phe448= (c.1344C>T) pathogenic?

TANC2 p.Phe448= (c.1344C>T) is classified Likely benign in TANC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-06). Ultra-rare (popmax 0.0533%, amr); Associated with TANC2-related disorder.

What condition is associated with TANC2 p.Phe448= (c.1344C>T)?

TANC2 p.Phe448= (c.1344C>T) is associated with TANC2-related disorder (ClinVar).

How common is TANC2 p.Phe448= (c.1344C>T) in the general population?

TANC2 p.Phe448= (c.1344C>T) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

TANC2 p.Phe448=

c.1344C>T · rs770439367 · VCV3034648

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Conditions

TANC2-related disorder

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 -8.4	GERP -5.3
Overall
CADD	1.723	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% Admixed American · 32/59,994 alleles

Filtering AF 0.0388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00316% 51/1,613,836 alleles · ultra-rare exomes 22/1,461,664 · genomes 29/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,875
Remaining individualsnot grpmax-eligible	0.0144%	6,940
African / African-American	0.00267%	37,460
South Asian	0.0022%	45,541
European (non-Finnish)	0.000509%	196,645

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.Phe448=
Coding: c.1344C>T
MANE Select: NM_001394998
dbSNP: rs770439367
Type: single nucleotide variant
Location: chr17:63314572 (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

Disease context

TANC2-related disorder

Similar variants

TANC2 p.Asp794Glu Uncertain significance ★★ ⚠ same condition
TANC2 p.Arg1443Cys Uncertain significance ★ ⚠ same condition
TANC2 p.Arg32Gly Uncertain significance ★ ⚠ same condition
TANC2 p.Gln874Arg Uncertain significance ★ ⚠ same condition
TANC2 p.Glu318Asp Uncertain significance ★ ⚠ same condition
TANC2 p.Lys648Glu Uncertain significance ★ ⚠ same condition
TANC2 p.Ser1828Cys Uncertain significance ★ ⚠ same condition
TANC2 p.Tyr562Cys Uncertain significance ★ ⚠ same condition

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-phe448 (accessed [today's date]).

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