Is TRAF7 p.Ser620Phe (c.1859C>T) pathogenic?

TRAF7 p.Ser620Phe (c.1859C>T) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TRAF7 p.Ser620Phe (c.1859C>T)?

TRAF7 p.Ser620Phe (c.1859C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TRAF7 p.Ser620Phe (c.1859C>T) in the general population?

TRAF7 p.Ser620Phe (c.1859C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF7 p.Ser620Phe (c.1859C>T)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

TRAF7 p.Ser620Phe

c.1859C>T · VCV4633495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 5% in TRAF7
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -15.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 1,993 bp · p 1.7e-10 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAF7
Protein: p.Ser620Phe
Coding: c.1859C>T
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2176161 (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-ser620phe (accessed [today's date]).

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