Is TRAF7 p.Ala660fs (c.1974_1975del) pathogenic?

TRAF7 p.Ala660fs (c.19741975del) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). Very rare (popmax 6.22e-05%).

How common is TRAF7 p.Ala660fs (c.1974_1975del) in the general population?

TRAF7 p.Ala660fs (c.1974_1975del) is very rare (popmax 6.22e-05%) (gnomAD).

TRAF7 p.Ala660fs

c.1974_1975del · rs2141299318 · VCV1702556

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (20 of 21, 24 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,606,800 alleles · very rare exomes 1/1,454,438 · genomes 0/152,362 · joint denominator

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: TRAF7
Protein: p.Ala660fs
Coding: c.1974_1975del
MANE Select: NM_032271
dbSNP: rs2141299318
Type: Deletion
Location: chr16:2176360 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB

Full TRAF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAF7 c.81+5_81+13del Benign/Likely benign ★★ same type
TRAF7 p.Glu515del Likely pathogenic ★ same type
TRAF7 c.348+2del Uncertain significance ★ same type
TRAF7 p.Asn468fs Uncertain significance ★ same type
TRAF7 p.Leu410fs Uncertain significance ★ same type
TRAF7 p.Ser494del Uncertain significance ★ same type
TRAF7 p.Pro22_Thr25del Benign ★ same type
TRAF7 c.1346+9_1346+33del Likely benign 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/traf7-p-ala660fs (accessed [today's date]).

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