Is TRAF7 p.Arg8His (c.23G>A) pathogenic?

TRAF7 p.Arg8His (c.23G>A) is classified Likely benign in TRAF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.1565); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with TRAF7 p.Arg8His (c.23G>A)?

TRAF7 p.Arg8His (c.23G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRAF7 p.Arg8His (c.23G>A) in the general population?

TRAF7 p.Arg8His (c.23G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about TRAF7 p.Arg8His (c.23G>A)?

AlphaMissense predicts likely benign (score 0.1565) — an in-silico prediction, not a clinical call.

TRAF7 p.Arg8His

c.23G>A · VCV4189837

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1565	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.38	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 4.2	GERP -1.5, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 7,404 bp · p 0.00052 · regional, not allelic
Overall
CADD	23.0	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 0.0111% East Asian · 5/44,846 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00592%

Overall 0.00645% 104/1,612,582 alleles · ultra-rare exomes 97/1,460,558 · genomes 7/152,024 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,969
European (non-Finnish)	0.00771%	12,964
Remaining individualsnot grpmax-eligible	0.0032%	31,226
Finnishnot grpmax-eligible	0.00317%	31,591
South Asian	0.0022%	45,486
Admixed American	0.00167%	59,932
African / African-American	0.00134%	74,872

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.Arg8His
Coding: c.23G>A
MANE Select: NM_032271
Type: single nucleotide variant
Location: chr16:2163943 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.16 · 1 PDB
Residue 8: 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-arg8his (accessed [today's date]).

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