Is TSFM p.Ter326= (c.978G>A) pathogenic?

TSFM p.Ter326= (c.978G>A) is classified Conflicting classifications of pathogenicity in TSFM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0384%, mid).

How common is TSFM p.Ter326= (c.978G>A) in the general population?

TSFM p.Ter326= (c.978G>A) is ultra-rare (popmax 0.0384%, mid) (gnomAD).

TSFM p.Ter326=

c.978G>A · rs766301009 · VCV1305295

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 2.3, phastCons 1
Overall
CADD	8.287	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% Middle Eastern · 2/5,214 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0104%

Overall 0.0033% 46/1,393,550 alleles · ultra-rare exomes 42/1,241,236 · genomes 4/152,314 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0384%	2,607
South Asian	0.0241%	4,155
Remaining individualsnot grpmax-eligible	0.0076%	13,163
European (non-Finnish)	0.00272%	36,760

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: TSFM
Protein: p.Ter326=
Coding: c.978G>A
MANE Select: NM_005726
dbSNP: rs766301009
Type: single nucleotide variant
Location: chr12:57796583 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.87 · 1 PDB

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

Similar variants

TSFM c.231+1G>A Likely pathogenic ★★ same type
TSFM c.232-2A>G Likely pathogenic ★★ same type
TSFM c.484-1G>A Likely pathogenic ★★ same type
TSFM c.484-1G>T Likely pathogenic ★★ same type
TSFM c.57+1G>A Likely pathogenic ★★ same type
TSFM c.571+1G>C Pathogenic/Likely pathogenic ★★ same type
TSFM p.Arg201Ter Pathogenic/Likely pathogenic ★★ same type
TSFM p.Arg312Trp Pathogenic/Likely pathogenic ★★ 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/tsfm-p-ter326 (accessed [today's date]).

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