Is TRAF7 p.Ile269= (c.807C>T) pathogenic?

TRAF7 p.Ile269= (c.807C>T) is classified Likely benign in TRAF7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-05-17). Ultra-rare (popmax 0.0331%, mid); Associated with TRAF7-related disorder.

What condition is associated with TRAF7 p.Ile269= (c.807C>T)?

TRAF7 p.Ile269= (c.807C>T) is associated with TRAF7-related disorder (ClinVar).

How common is TRAF7 p.Ile269= (c.807C>T) in the general population?

TRAF7 p.Ile269= (c.807C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

TRAF7 p.Ile269=

c.807C>T · rs560235497 · VCV3042227

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Conditions

TRAF7-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.8	GERP -4.6
Overall
CADD	7.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,048 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00199% 32/1,609,078 alleles · ultra-rare exomes 23/1,456,950 · genomes 9/152,128 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,024
African / African-American	0.00668%	14,973
South Asian	0.00442%	22,632
Admixed American	0.00335%	29,811
East Asian	0.00224%	44,706
Remaining individualsnot grpmax-eligible	0.0016%	62,354
European (non-Finnish)	0.00144%	69,331

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.Ile269=
Coding: c.807C>T
MANE Select: NM_032271
dbSNP: rs560235497
Type: single nucleotide variant
Location: chr16:2173194 (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

Disease context

TRAF7-related disorder

Similar variants

TRAF7 p.Arg524Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRAF7 p.Arg655Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRAF7 p.Leu625Phe Likely pathogenic ★ same condition
TRAF7 p.Phe617Ser Likely pathogenic ★ same condition
TRAF7 p.Ser663Thr Likely pathogenic ★ ⚠ same condition
TRAF7 c.1346+3G>A Uncertain significance ★ same condition
TRAF7 p.Arg547Ter Uncertain significance ★ same condition
TRAF7 p.His299Gln 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/traf7-p-ile269 (accessed [today's date]).

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