Is TRAF7 p.Met1Val (c.1A>G) pathogenic?

TRAF7 p.Met1Val (c.1A>G) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). Very rare (popmax 0.00669%, eas).

How common is TRAF7 p.Met1Val (c.1A>G) in the general population?

TRAF7 p.Met1Val (c.1A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

TRAF7 p.Met1Val

c.1A>G · rs2093067299 · VCV1801084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.237	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.6	GERP 0.22, phastCons 1
Overall
CADD	21.2	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 0.00669% East Asian · 3/44,834 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000248% 4/1,612,198 alleles · very rare exomes 4/1,460,046 · genomes 0/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,945
European (non-Finnish)	8.48e-05%	1,179,526

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.Met1Val
Coding: c.1A>G
MANE Select: NM_032271
dbSNP: rs2093067299
Type: single nucleotide variant
Location: chr16:2163921 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB
Residue 1: the 'disordered' region

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

Similar variants

TRAF7 p.Arg524Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Arg655Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Leu402Val Pathogenic ★★ ⚠ same type
TRAF7 p.Leu625Val Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Ser558Phe Pathogenic ★★ ⚠ same type
TRAF7 p.Ser629Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
TRAF7 p.Arg316Cys Uncertain significance ★★ ⚠ same type
TRAF7 p.Arg371Trp 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/traf7-p-met1val (accessed [today's date]).

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