Is TRAF7 p.Ala606Val (c.1817C>T) pathogenic?

TRAF7 p.Ala606Val (c.1817C>T) is classified Likely benign in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely pathogenic (0.919); Very rare (popmax 0.00449%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TRAF7 p.Ala606Val (c.1817C>T)?

TRAF7 p.Ala606Val (c.1817C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAF7 p.Ala606Val (c.1817C>T) in the general population?

TRAF7 p.Ala606Val (c.1817C>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about TRAF7 p.Ala606Val (c.1817C>T)?

AlphaMissense predicts likely pathogenic (score 0.919) — an in-silico prediction, not a clinical call.

TRAF7 p.Ala606Val

c.1817C>T · VCV3328438

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.919	likely pathogenic
REVEL	0.358	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,993 bp · p 1.7e-10 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,179,546 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00366% 59/1,610,786 alleles · very rare exomes 57/1,458,560 · genomes 2/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,256
Finnishnot grpmax-eligible	0.00325%	30,799
East Asian	0.00223%	44,870
Admixed American	0.00167%	59,910
Remaining individualsnot grpmax-eligible	0.0016%	62,392
South Asian	0.0011%	90,976

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.Ala606Val
Coding: c.1817C>T
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2176119 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAF7 p.Arg316Cys Uncertain significance ★★ ⚠ same condition
TRAF7 p.Lys615Arg Uncertain significance ★★ ⚠ same condition
TRAF7 p.Thr267Met Uncertain significance ★★ ⚠ same condition
TRAF7 p.Pro70= Likely benign ★★ same condition
TRAF7 p.Ser51Asn Likely benign ★★ same condition
TRAF7 p.Ala122Val Uncertain significance ★ ⚠ same condition
TRAF7 p.Ala176Thr Uncertain significance ★ ⚠ same condition
TRAF7 p.Ala218Ser 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-ala606val (accessed [today's date]).

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