Is TRAFD1 p.Pro301Arg (c.902C>G) pathogenic?

TRAFD1 p.Pro301Arg (c.902C>G) is classified Uncertain significance in TRAFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.3346); Very rare (popmax 0.00267%, afr).

How common is TRAFD1 p.Pro301Arg (c.902C>G) in the general population?

TRAFD1 p.Pro301Arg (c.902C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about TRAFD1 p.Pro301Arg (c.902C>G)?

AlphaMissense predicts likely benign (score 0.3346) — an in-silico prediction, not a clinical call.

TRAFD1 p.Pro301Arg

c.902C>G · VCV4189848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3346 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3346	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -10.64	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 0.0022 · regional, not allelic
Overall
CADD	27.9	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 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,974 alleles · very rare exomes 1/1,461,846 · genomes 1/152,128 · joint denominator

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: TRAFD1
Protein: p.Pro301Arg
Coding: c.902C>G
MANE Select: NM_006700
Type: single nucleotide variant
Location: chr12:112145637 (GRCh38)
Gene constraint: LOEUF 0.749 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.45 · 1 PDB

Full TRAFD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAFD1 p.Ala56Thr Uncertain significance ★★ ⚠ same type
TRAFD1 p.Glu232= Benign ★★ same type
TRAFD1 p.Ala147Thr Uncertain significance ★ ⚠ same type
TRAFD1 p.Ala258Thr Uncertain significance ★ ⚠ same type
TRAFD1 p.Ala317Thr Uncertain significance ★ ⚠ same type
TRAFD1 p.Ala505Val Uncertain significance ★ ⚠ same type
TRAFD1 p.Ala554Ser Uncertain significance ★ ⚠ same type
TRAFD1 p.Arg112Trp Uncertain significance ★ ⚠ same type

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/trafd1-p-pro301arg (accessed [today's date]).

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