Is TRAFD1 p.Arg264Ser (c.792G>C) pathogenic?

TRAFD1 p.Arg264Ser (c.792G>C) is classified Uncertain significance in TRAFD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-27). AlphaMissense: likely benign (0.1591); Rare (popmax 0.136%, afr).

How common is TRAFD1 p.Arg264Ser (c.792G>C) in the general population?

TRAFD1 p.Arg264Ser (c.792G>C) is rare (popmax 0.136%, afr) (gnomAD).

What do computational predictors say about TRAFD1 p.Arg264Ser (c.792G>C)?

AlphaMissense predicts likely benign (score 0.1591) — an in-silico prediction, not a clinical call.

TRAFD1 p.Arg264Ser

c.792G>C · VCV3809985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1591 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1591	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.82	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 1.1	GERP -1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 0.0022 · regional, not allelic
Overall
CADD	20.2	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 0.136% African / African-American · 102/75,014 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.00694% 112/1,613,920 alleles · rare exomes 59/1,461,718 · genomes 53/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.136%	735
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0064%	15,623
Admixed American	0.005%	19,996
European (non-Finnish)	8.48e-05%	1,179,908

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.Arg264Ser
Coding: c.792G>C
MANE Select: NM_006700
Type: single nucleotide variant
Location: chr12:112142237 (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-arg264ser (accessed [today's date]).

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