Is TRAF7 p.Ser69Pro (c.205T>C) pathogenic?

TRAF7 p.Ser69Pro (c.205T>C) is classified Uncertain significance in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-21). AlphaMissense: likely benign (0.1132); Very rare (popmax 0.00879%, sas); Associated with Inborn genetic diseases.

What condition is associated with TRAF7 p.Ser69Pro (c.205T>C)?

TRAF7 p.Ser69Pro (c.205T>C) is associated with Inborn genetic diseases (ClinVar).

How common is TRAF7 p.Ser69Pro (c.205T>C) in the general population?

TRAF7 p.Ser69Pro (c.205T>C) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about TRAF7 p.Ser69Pro (c.205T>C)?

AlphaMissense predicts likely benign (score 0.1132) — an in-silico prediction, not a clinical call.

TRAF7 p.Ser69Pro

c.205T>C · rs765305848 · VCV2328826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1132	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.029, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 7,404 bp · p 0.00052 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00879% South Asian · 8/91,004 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000869% 14/1,611,714 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,376
Admixed American	0.00834%	11,989
European (non-Finnish)	8.48e-05%	1,179,742

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.Ser69Pro
Coding: c.205T>C
MANE Select: NM_032271
dbSNP: rs765305848
Type: single nucleotide variant
Location: chr16:2168142 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB
Residue 69: 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.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-ser69pro (accessed [today's date]).

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