Is TRAF7 p.Ser86Pro (c.256T>C) pathogenic?

TRAF7 p.Ser86Pro (c.256T>C) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: ambiguous (0.355); Very rare (popmax 0.00222%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRAF7 p.Ser86Pro (c.256T>C)?

TRAF7 p.Ser86Pro (c.256T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRAF7 p.Ser86Pro (c.256T>C) in the general population?

TRAF7 p.Ser86Pro (c.256T>C) is very rare (popmax 0.00222%, sas) (gnomAD).

What do computational predictors say about TRAF7 p.Ser86Pro (c.256T>C)?

AlphaMissense predicts ambiguous (score 0.355) — an in-silico prediction, not a clinical call.

TRAF7 p.Ser86Pro

c.256T>C · VCV3328439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.355 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.355	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -8.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 7,404 bp · p 0.00052 · regional, not allelic
Overall
CADD	28.3	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 0.00222% South Asian · 2/90,284 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000124% 2/1,609,886 alleles · very rare

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.Ser86Pro
Coding: c.256T>C
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2170638 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB
Residue 86: the 'disordered' region

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.Ser86= Likely benign ★ same residue
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

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-ser86pro (accessed [today's date]).

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